Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
April-2026 Volume 33 Issue 4

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
April-2026 Volume 33 Issue 4

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Review Open Access

Prostate‑specific membrane antigen: Molecular functions and emerging roles as a therapeutic target (Review)

  • Authors:
    • Ryuta Watanabe
    • Tomohisa Sakaue
    • Noriyoshi Miura
    • Tadahiko Kikugawa
    • Takashi Saika
  • View Affiliations / Copyright

    Affiliations: Department of Urology, Ehime University Hospital, Toon, Ehime 791‑0295, Japan, Department of Cardiovascular and Thoracic Surgery, Ehime University Graduate School of Medicine, Toon, Ehime 791‑0295, Japan
    Copyright: © Watanabe et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 122
    |
    Published online on: February 26, 2026
       https://doi.org/10.3892/mmr.2026.13832
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:


Abstract

The present review focuses on the molecular functions of prostate‑specific membrane antigen (PSMA) as a biologically active protein. Its clinical use as a positron emission tomography imaging marker or radioligand therapy target is beyond the scope of the current review. The role of PSMA (also known as folate hydrolase 1/glutamate carboxypeptidase II/N‑acetylated‑α‑linked acidic dipeptidase) has progressed from that of a prostate cancer biomarker to a functional driver of tumor biology. Structurally, PSMA is a type II transmembrane glycoprotein with glutamate carboxypeptidase and folate hydrolase activities, linking glutamate and one‑carbon metabolism to proliferation, redox balance and epigenetic regulation. PSMA undergoes clathrin‑dependent endocytosis and interacts with various scaffolding proteins, such as filamin A and receptor for activated C kinase 1, which are properties that underlie its functional role as a molecular signaling hub, in addition to being a therapeutic entry point. Its expression is dynamically regulated by androgen receptor signaling, NF‑κB activation and epigenetic modifiers, contributing to intra‑patient heterogeneity and treatment resistance. PSMA expression is not restricted to prostate epithelium but is also expressed in tumor‑associated endothelium across multiple malignancies, where it can promote angiogenesis through integrin/PI3K‑AKT‑mTOR signaling and paracrine induction by extracellular vesicles. These molecular functions can result in immune exclusion, stromal activation and neuronal interactions, positioning PSMA as a key regulator of the tumor microenvironment. Although PSMA‑targeted imaging and therapies have demonstrated substantial clinical utility, understanding the biological basis of the function of PSMA is essential for interpreting the heterogeneous clinical responses and for designing next‑generation therapeutic strategies in association with this protein. By integrating enzymatic activity, non‑enzymatic scaffold signaling and tumor microenvironmental regulatory information, the present review provides a functional framework in the PSMA biology field and discusses how these molecular properties can be leveraged to develop novel rational and effective PSMA‑targeted interventions.
View Figures

Figure 1

Integrated schematic of PSMA
molecular functions and therapeutic implications. (A) Enzymatic
features. PSMA structure and enzymatic activities in the (Aa) brain
and (Ab) intestine, linking glutamate signaling and folate
metabolism. (B) Endothelial expression across cancer types. PSMA
expression in tumor-associated vascular endothelium and its role in
tumor angiogenesis. (C) Regulation of signaling pathways. PSMA
functions as a signaling hub through interactions with integrins
and other membrane proteins. (D) Internalization and recycling.
Ligand-induced internalization and recycling of PSMA, enabling
targeted therapy and sustained surface signaling. This schematic
illustration was created with the support of Medical Fig
(https://medicalfig.medicaleducation.co.jp/). AP-2,
adaptor protein 2; ECM, extracellular matrix; F, folate; G,
glutamate; IGF-1R, insulin-like growth factor 1 receptor; mGluR,
metabotropic glutamate receptor; NAAG, N-acetylaspartylglutamate;
NSCLC, non-small cell lung cancer; PSMA, prostate-specific membrane
antigen; RACK1, receptor for activated C kinase 1; RFC, reduced
folate carrier; RLT, radioligand therapy; TCA cycle, tricarboxylic
acid cycle.

Figure 2

Immunohistochemical detection of PSMA
in the tumor-associated vasculature of genitourinary malignancies.
Representative immunohistochemical images from 3 genitourinary
cancer cases using surgically resected specimens obtained during
routine clinical care as part of the present study: Case 1, renal
cell carcinoma; case 2, upper tract urothelial carcinoma; and case
3, bladder cancer. All cases exhibited PSMA expression in
tumor-associated blood vessels. PSMA-positive endothelial cells are
highlighted by red arrowheads and were predominantly localized in
the tumor-associated vasculature surrounding tumor nests, whereas
adjacent normal vessels remained negative. Formalin-fixed,
paraffin-embedded sections (3–5 µm) were stained with a mouse
monoclonal anti-PSMA antibody (M3620; Dako; Agilent Technologies,
Inc.). Endothelial PSMA positivity was defined as distinct
membranous and/or cytoplasmic staining in tumor-associated blood
vessels. Magnification, ×400; scale bar, 50 µm. PSMA,
prostate-specific membrane antigen.

Figure 3

Proposed model of PSMA-associated
angiogenic signaling in the tumor microenvironment. Schematic model
illustrating how tumor-derived extracellular vesicles modulate the
tumor microenvironment and induce PSMA upregulation in
tumor-associated endothelial cells. PSMA-positive endothelial
cells, together with other stromal components such as CAFs and
TAMs, contribute to the release of pro-angiogenic factors and
activation of scaffold-mediated signaling, thereby promoting
endothelial activation and angiogenic sprouting. This schematic
illustration was created with the support of Medical Fig
(https://medicalfig.medicaleducation.co.jp/). CAF,
cancer-associated fibroblast; IGF-1R, insulin-like growth factor 1
receptor; RACK1, receptor for activated C kinase 1; PSMA,
prostate-specific membrane antigen; TAM, tumor-associated
macrophage.
View References

1 

Maes J, Gesquière S, De Spiegeleer A, Maes A and Van de Wiele C: Prostate-specific membrane antigen biology and pathophysiology in prostate carcinoma, an update: Potential implications for targeted imaging and therapy. Int J Mol Sci. 25:97552024. View Article : Google Scholar

2 

Hyväkkä A, Virtanen V, Kemppainen J, Grönroos TJ, Minn H and Sundvall M: More than meets the eye: Scientific rationale behind molecular imaging and therapeutic targeting of prostate-specific membrane antigen (PSMA) in metastatic prostate cancer and beyond. Cancers (Basel). 13:22442021. View Article : Google Scholar

3 

Haffner MC, Kronberger IE, Ross JS, Sheehan CE, Zitt M, Mühlmann G, Ofner D, Zelger B, Ensinger C, Yang XJ, et al: Prostate-specific membrane antigen expression in the neovasculature of gastric and colorectal cancers. Hum Pathol. 40:1754–1761. 2009. View Article : Google Scholar

4 

Van de Wiele C, Sathekge M, de Spiegeleer B, De Jonghe PJ, Debruyne PR, Borms M, Beels L and Maes A: PSMA expression on neovasculature of solid tumors. Histol Histopathol. 35:919–927. 2020.

5 

Watanabe R, Maekawa M, Kiyoi T, Kurata M, Miura N, Kikugawa T, Higashiyama S and Saika T: PSMA-positive membranes secreted from prostate cancer cells have potency to transform vascular endothelial cells into an angiogenic state. Prostate. 81:1390–1401. 2021. View Article : Google Scholar : PubMed/NCBI

6 

Watanabe R, Kagimoto K, Chosei M, Sakaue T, Kurata M, Miura N, Kitazawa R, Kikugawa T, Higashiyama S and Saika T: Vesicles secreted by renal cell carcinoma cells cause vascular endothelial cells to express PSMA and drive tumor progression. Cells. 14:1652025. View Article : Google Scholar : PubMed/NCBI

7 

Israeli RS, Powell CT, Fair WR and Heston WD: Molecular cloning of a complementary DNA encoding a prostate-specific membrane antigen. Cancer Res. 53:227–230. 1993.PubMed/NCBI

8 

Bzdega T, Turi T, Wroblewska B, She D, Chung HS, Kim H and Neale JH: Molecular cloning of a peptidase against N-acetylaspartylglutamate from a rat hippocampal cDNA library. J Neurochem. 69:2270–2277. 1997. View Article : Google Scholar : PubMed/NCBI

9 

Pinto JT, Suffoletto BP, Berzin TM, Qiao CH, Lin S, Tong WP, May F, Mukherjee B and Heston WD: Prostate-specific membrane antigen: A novel folate hydrolase in human prostatic carcinoma cells. Clin Cancer Res. 2:1445–1451. 1996.PubMed/NCBI

10 

Davis MI, Bennett MJ, Thomas LM and Bjorkman PJ: Crystal structure of prostate-specific membrane antigen, a tumor marker and peptidase. Proc Natl Acad Sci USA. 102:5981–5986. 2005. View Article : Google Scholar : PubMed/NCBI

11 

Barinka C, Rovenská M, Mlcochová P, Hlouchová K, Plechanovová A, Majer P, Tsukamoto T, Slusher BS, Konvalinka J and Lubkowski J: Structural insight into the pharmacophore pocket of human glutamate carboxypeptidase II. J Med Chem. 50:3267–3273. 2007. View Article : Google Scholar : PubMed/NCBI

12 

Liu H, Rajasekaran AK, Moy P, Xia Y, Kim S, Navarro V, Rahmati R and Bander NH: Constitutive and antibody-induced internalization of prostate-specific membrane antigen. Cancer Res. 58:4055–4060. 1998.PubMed/NCBI

13 

Anilkumar G, Rajasekaran SA, Wang S, Hankinson O, Bander NH and Rajasekaran AK: Prostate-specific membrane antigen association with filamin A modulates its internalization and NAALADase activity. Cancer Res. 63:2645–2648. 2003.PubMed/NCBI

14 

Tsai G, Passani LA, Slusher BS, Carter R, Baer L, Kleinman JE and Coyle JT: Abnormal excitatory neurotransmitter metabolism in schizophrenic brains. Arch Gen Psychiatry. 52:829–836. 1995. View Article : Google Scholar : PubMed/NCBI

15 

Slusher BS, Vornov JJ, Thomas AG, Hurn PD, Harukuni I, Bhardwaj A, Traystman RJ, Robinson MB, Britton P, Lu XC, et al: Selective inhibition of NAALADase, which converts NAAG to glutamate, reduces ischemic brain injury. Nat Med. 5:1396–1402. 1999. View Article : Google Scholar : PubMed/NCBI

16 

Caromile LA, Dortche K, Rahman MM, Grant CL, Stoddard C, Ferrer FA and Shapiro LH: PSMA redirects cell survival signaling from the MAPK to the PI3K-AKT pathways to promote the progression of prostate cancer. Sci Signal. 10:eaag33262017. View Article : Google Scholar

17 

Boixareu C, Taha T, Venkadakrishnan VB, de Bono J and Beltran H: Targeting the tumour cell surface in advanced prostate cancer. Nat Rev Urol. 22:569–589. 2025. View Article : Google Scholar

18 

Sedlák F, Kvasnička A, Marešová B, Brumarová R, Dobešová D, Dostálová K, Šrámková K, Pehr M, Šácha P, Friedecký D and Konvalinka J: Parallel metabolomics and lipidomics of a PSMA/GCPII deficient mouse model reveal alteration of NAAG levels and brain lipid composition. ACS Chem Neurosci. 15:1342–1355. 2024. View Article : Google Scholar

19 

Pellegrino S and Fonti R: A look into the future: The role of PSMA beyond prostate cancer. Eur J Nucl Med Mol Imaging. 51:278–280. 2023. View Article : Google Scholar : PubMed/NCBI

20 

Rajasekaran SA, Anilkumar G, Oshima E, Bowie JU, Liu H, Heston W, Bander NH and Rajasekaran AK: A novel cytoplasmic tail MXXXL motif mediates the internalization of prostate-specific membrane antigen. Mol Biol Cell. 14:4835–4845. 2003. View Article : Google Scholar

21 

Zhang X, Qi S, Liu D, Du J and Jin J: PSMA-Targeted supramolecular nanoparticles prepared from cucurbit[8]uril-based ternary host-guest recognition for prostate cancer therapy. Front Chem. 10:8475232022. View Article : Google Scholar : PubMed/NCBI

22 

Minner S, Wittmer C, Graefen M, Salomon G, Steuber T, Haese A, Huland H, Bokemeyer C, Yekebas E, Dierlamm J, et al: High level PSMA expression is associated with early PSA recurrence in surgically treated prostate cancer. Prostate. 71:281–288. 2011. View Article : Google Scholar : PubMed/NCBI

23 

Meller B, Bremmer F, Sahlmann CO, Hijazi S, Bouter C, Trojan L, Meller J and Thelen P: Alterations in androgen deprivation enhanced prostate-specific membrane antigen (PSMA) expression in prostate cancer cells as a target for diagnostics and therapy. EJNMMI Res. 5:662015. View Article : Google Scholar : PubMed/NCBI

24 

Calais J, Kishan AU, Cao M, Fendler WP, Eiber M, Herrmann K, Ceci F, Reiter RE, Rettig MB, Hegde JV, et al: Potential impact of 68Ga-PSMA-11 PET/CT on the planning of definitive radiation therapy for prostate cancer. J Nucl Med. 59:1714–1721. 2018. View Article : Google Scholar : PubMed/NCBI

25 

Staal J and Beyaert R: Inflammation and NF-κB signaling in prostate cancer: Mechanisms and clinical implications. Cells. 7:1222018. View Article : Google Scholar : PubMed/NCBI

26 

Basílio J, Hochreiter B, Hoesel B, Sheshori E, Mussbacher M, Hanel R and Schmid JA: Antagonistic functions of androgen receptor and NF-κB in prostate cancer-experimental and computational analyses. Cancers (Basel). 14:61642022. View Article : Google Scholar

27 

Watt F, Martorana A, Brookes DE, Ho T, Kingsley E, O'Keefe DS, Russell PJ, Heston WD and Molloy PL: A tissue-specific enhancer of the prostate-specific membrane antigen gene, FOLH1. Genomics. 73:243–254. 2001. View Article : Google Scholar : PubMed/NCBI

28 

Noss KR, Wolfe SA and Grimes SR: Upregulation of prostate specific membrane antigen/folate hydrolase transcription by an enhancer. Gene. 285:247–256. 2002. View Article : Google Scholar : PubMed/NCBI

29 

Gao Y, Zheng H, Li L, Feng M, Chen X, Hao B, Lv Z, Zhou X and Cao Y: Prostate-specific membrane antigen (PSMA) promotes angiogenesis of glioblastoma through interacting with ITGB4 and regulating NF-κB signaling pathway. Front Cell Dev Biol. 9:5983772021. View Article : Google Scholar

30 

Perico ME, Grasso S, Brunelli M, Martignoni G, Munari E, Moiso E, Fracasso G, Cestari T, Naim HY, Bronte V, et al: Prostate-specific membrane antigen (PSMA) assembles a macromolecular complex regulating growth and survival of prostate cancer cells ‘in vitro’ and correlating with progression ‘in vivo’. Oncotarget. 7:74189–74202. 2016. View Article : Google Scholar

31 

Ghosh A, Wang X, Klein E and Heston WD: Novel role of prostate-specific membrane antigen in suppressing prostate cancer invasiveness. Cancer Res. 65:727–731. 2005. View Article : Google Scholar : PubMed/NCBI

32 

Silver DA, Pellicer I, Fair WR, Heston WD and Cordon-Cardo C: Prostate-specific membrane antigen expression in normal and malignant human tissues. Clin Cancer Res. 3:81–85. 1997.PubMed/NCBI

33 

Bakht MK, Yamada Y, Ku SY, Venkadakrishnan VB, Korsen JA, Kalidindi TM, Mizuno K, Ahn SH, Seo JH, Garcia MM, et al: Landscape of prostate-specific membrane antigen heterogeneity and regulation in AR-positive and AR-negative metastatic prostate cancer. Nat Cancer. 4:699–715. 2023. View Article : Google Scholar : PubMed/NCBI

34 

Damjanovic J, Janssen JC, Prasad V, Diederichs G, Walter T, Brenner W and Makowski MR: 68Ga-PSMA-PET/CT for the evaluation of liver metastases in patients with prostate cancer. Cancer Imaging. 19:372019. View Article : Google Scholar : PubMed/NCBI

35 

Mattoni S, Farolfi A, Formaggio F, Bruno G, Caroli P, Cerci JJ, Eiber M, Fendler WP, Golfieri R, Herrmann K, et al: PSMA PET for the evaluation of liver metastases in castration-resistant prostate cancer patients: A multicenter retrospective study. Cancers (Basel). 14:56802022. View Article : Google Scholar : PubMed/NCBI

36 

Sayar E, Patel RA, Coleman IM, Roudier MP, Zhang A, Mustafi P, Low JY, Hanratty B, Ang LS, Bhatia V, et al: Reversible epigenetic alterations mediate PSMA expression heterogeneity in advanced metastatic prostate cancer. JCI Insight. 8:e1629072023. View Article : Google Scholar

37 

Hope TA, Eiber M, Armstrong WR, Juarez R, Murthy V, Lawhn-Heath C, Behr SC, Zhang L, Barbato F, Ceci F, et al: Diagnostic accuracy of 68Ga-PSMA-11 PET for pelvic nodal metastasis detection prior to radical prostatectomy and pelvic lymph node dissection: A multicenter prospective phase 3 imaging trial. JAMA Oncol. 7:1635–1642. 2021. View Article : Google Scholar

38 

Wernicke AG, Edgar MA, Lavi E, Liu H, Salerno P, Bander NH and Gutin PH: Prostate-specific membrane antigen as a potential novel vascular target for treatment of glioblastoma multiforme. Arch Pathol Lab Med. 135:1486–1489. 2011. View Article : Google Scholar : PubMed/NCBI

39 

Fragomeni RA, Amir T, Sheikhbahaei S, Harvey SC, Javadi MS, Solnes LB, Kiess AP, Allaf ME, Pomper MG, Gorin MA and Rowe SP: Imaging of nonprostate cancers using PSMA-targeted radiotracers: Rationale, current state of the field, and a call to arms. J Nucl Med. 59:871–877. 2018. View Article : Google Scholar : PubMed/NCBI

40 

Moore M, Panjwani S, Mathew R, Crowley M, Liu YF, Aronova A, Finnerty B, Zarnegar R, Fahey TJ III and Scognamiglio T: Well-differentiated thyroid cancer neovasculature expresses prostate-specific membrane antigen-a possible novel therapeutic target. Endocr Pathol. 28:339–344. 2017. View Article : Google Scholar

41 

Nomura N, Pastorino S, Jiang P, Lambert G, Crawford JR, Gymnopoulos M, Piccioni D, Juarez T, Pingle SC, Makale M and Kesari S: Prostate specific membrane antigen (PSMA) expression in primary gliomas and breast cancer brain metastases. Cancer Cell Int. 14:262014. View Article : Google Scholar

42 

Bychkov A, Vutrapongwatana U, Tepmongkol S and Keelawat S: PSMA expression by microvasculature of thyroid tumors-Potential implications for PSMA theranostics. Sci Rep. 7:52022017. View Article : Google Scholar : PubMed/NCBI

43 

Kasoha M, Unger C, Solomayer EF, Bohle RM, Zaharia C, Khreich F, Wagenpfeil S and Juhasz-Böss I: Prostate-specific membrane antigen (PSMA) expression in breast cancer and its metastases. Clin Exp Metastasis. 34:479–490. 2017. View Article : Google Scholar : PubMed/NCBI

44 

Schmidt LH, Heitkötter B, Schulze AB, Schliemann C, Steinestel K, Trautmann M, Marra A, Hillejan L, Mohr M, Evers G, et al: Prostate specific membrane antigen (PSMA) expression in non-small cell lung cancer. PLoS One. 12:e01862802017. View Article : Google Scholar : PubMed/NCBI

45 

Machado CML, Skubal M, Haedicke K, Silva FP, Stater EP, Silva TLAO, Costa ET, Masotti C, Otake AH, Andrade LNS, et al: Membrane-derived particles shed by PSMA-positive cells function as pro-angiogenic stimuli in tumors. J Control Release. 364:312–325. 2023. View Article : Google Scholar : PubMed/NCBI

46 

Conway RE, Petrovic N, Li Z, Heston W, Wu D and Shapiro LH: Prostate-specific membrane antigen regulates angiogenesis by modulating integrin signal transduction. Mol Cell Biol. 26:5310–5324. 2006. View Article : Google Scholar

47 

Grant CL, Caromile LA, Ho V, Durrani K, Rahman MM, Claffey KP, Fong GH and Shapiro LH: Prostate specific membrane antigen (PSMA) regulates angiogenesis independently of VEGF during ocular neovascularization. PLoS One. 7:e412852012. View Article : Google Scholar : PubMed/NCBI

48 

Li Y, Zhang K, Yang F, Jiao D, Li M, Zhao X, Xu C, Liu S, Li H, Shi S, et al: Prognostic value of vascular-expressed PSMA and CD248 in urothelial carcinoma of the bladder. Front Oncol. 11:7710362021. View Article : Google Scholar

49 

Schreiber H, Hänze J, Nimphius W, Verburg FA, Luster M, Hofmann R and Hegele A: Prostate specific membrane antigen (PSMA) in urothelial cell carcinoma (UCC) is associated with tumor grading and staging. J Cancer Res Clin Oncol. 146:305–313. 2020. View Article : Google Scholar

50 

Lin BH, Chen SH, Chen SM, Qiu QR, Gao RC, Wei Y, Zheng QS, Miao WB and Xu N: Head-to-head comparisons of 68Ga-PSMA-11 and 18F-FDG PET/CT in evaluating patients with upper tract urothelial carcinoma: A prospective pilot study. Int Urol Nephrol. 55:2753–2764. 2023. View Article : Google Scholar

51 

Liu D, Wang L and Guo Y: Advances in and prospects of immunotherapy for prostate cancer. Cancer Lett. 601:2171552024. View Article : Google Scholar

52 

Ge R, Wang Z and Cheng L: Tumor microenvironment heterogeneity an important mediator of prostate cancer progression and therapeutic resistance. NPJ Precis Oncol. 6:312022. View Article : Google Scholar

53 

Puik JR, Le C, Kazemier G, Oprea-Lager DE, Swijnenburg RJ, Giovannetti E, Griffioen AW and Huijbers EJ: Prostate-specific membrane antigen as target for vasculature-directed therapeutic strategies in solid tumors. Crit Rev Oncol Hematol. 205:1045562025. View Article : Google Scholar

54 

Maguid MS, Saad El Dine MG, Gabal SM and Fandoud SM: Prostate-specific membrane antigen (PSMA) expression in the neovasculature of high grade gliomas (Histopathological and Immunohistochemical Study). Asian Pac J Cancer Prev. 24:1797–1808. 2023. View Article : Google Scholar : PubMed/NCBI

55 

Bellavia MC, Patel RB and Anderson CJ: Combined targeted radiopharmaceutical therapy and immune checkpoint blockade: From preclinical advances to the clinic. J Nucl Med. 63:1636–1641. 2022.PubMed/NCBI

56 

Altunay B, Schäfer L, Morgenroth A, Peña Q, Lammers T, Saar M, Mottaghy FM and Lütje S: Combining PSMA-targeted radiopharmaceutical therapy with immunotherapy. J Nucl Med. 28:1522–1527. 2025. View Article : Google Scholar

57 

Jiao R and Dadachova E: Combination of radioligand therapy and immunotherapy: How to make it work in clinic? Immunotargets Ther. 14:755–759. 2025. View Article : Google Scholar : PubMed/NCBI

58 

Sheehan B, Guo C, Neeb A, Paschalis A, Sandhu S and de Bono JS: Prostate-specific membrane antigen biology in lethal prostate cancer and its therapeutic implications. Eur Urol Focus. 8:1157–1168. 2022. View Article : Google Scholar : PubMed/NCBI

59 

Palamiuc L and Emerling BM: PSMA brings new flavors to PI3K signaling: A role for glutamate in prostate cancer. J Exp Med. 215:17–19. 2018. View Article : Google Scholar : PubMed/NCBI

60 

O'Keefe DS, Bacich DJ, Huang SS and Heston WDW: A perspective on the evolving story of PSMA biology, PSMA-based imaging, and endoradiotherapeutic strategies. J Nucl Med. 59:1007–1013. 2018. View Article : Google Scholar

61 

Wright K, Ly T, Kriet M, Czirok A and Thomas SM: Cancer-associated fibroblasts: Master tumor microenvironment modifiers. Cancers (Basel). 15:18992023. View Article : Google Scholar : PubMed/NCBI

62 

Bonollo F, Thalmann GN, Kruithof-de Julio M and Karkampouna S: The role of cancer-associated fibroblasts in prostate cancer tumorigenesis. Cancers (Basel). 12:18872020. View Article : Google Scholar : PubMed/NCBI

63 

McBriar JD, Shafiian N, Scharf S, Boockvar JA and Wernicke AG: Prostate-specific membrane antigen use in glioma management: Past, present, and future. Clin Nucl Med. 49:806–816. 2024. View Article : Google Scholar : PubMed/NCBI

64 

Hameed MY, Gul M and Chaudhry A, Muzaffar H, Sheikh M, Chee W, Ayyash S, Ayyash J, Al-Hindi M, Shahare H and Chaudhry A: From oncogenesis to theranostics: The transformative role of PSMA in prostate cancer. Cancers (Basel). 16:30392024. View Article : Google Scholar : PubMed/NCBI

65 

Hofman MS, Lawrentschuk N, Francis RJ, Tang C, Vela I, Thomas P, Rutherford N, Martin JM, Frydenberg M, Shakher R, et al: Prostate-specific membrane antigen PET-CT in patients with high-risk prostate cancer before curative-intent surgery or radiotherapy (proPSMA): A prospective, randomised, multicentre study. Lancet. 395:1208–1216. 2020. View Article : Google Scholar

66 

de Galiza Barbosa F, Queiroz MA, Nunes RF, Costa LB, Zaniboni EC, Marin JFG, Cerri GG and Buchpiguel CA: Nonprostatic diseases on PSMA PET imaging: A spectrum of benign and malignant findings. Cancer Imaging. 20:232020. View Article : Google Scholar : PubMed/NCBI

67 

Sartor O, de Bono J, Chi KN, Fizazi K, Herrmann K, Rahbar K, Tagawa ST, Nordquist LT, Vaishampayan N, El-Haddad G, et al: Lutetium-177-PSMA-617 for metastatic castration-resistant prostate cancer. N Engl J Med. 385:1091–1103. 2021. View Article : Google Scholar : PubMed/NCBI

68 

Kratochwil C, Bruchertseifer F, Rathke H, Bronzel M, Apostolidis C, Weichert W, Haberkorn U, Giesel FL and Morgenstern A: Targeted α-therapy of metastatic castration-resistant prostate cancer with 225Ac-PSMA-617: Dosimetry estimate and empiric dose finding. J Nucl Med. 58:1624–1631. 2017. View Article : Google Scholar : PubMed/NCBI

69 

Sridaran D, Bradshaw E, DeSelm C, Pachynski R, Mahajan K and Mahajan NP: Prostate cancer immunotherapy: Improving clinical outcomes with a multi-pronged approach. Cell Rep Med. 4:1011992023. View Article : Google Scholar : PubMed/NCBI

70 

Ettala O, Malaspina S, Tuokkola T, Luoto P, Löyttyniemi E, Boström PJ and Kemppainen J: Prospective study on the effect of short-term androgen deprivation therapy on PSMA uptake evaluated with 68Ga-PSMA-11 PET/MRI in men with treatment-naïve prostate cancer. Eur J Nucl Med Mol Imaging. 47:665–673. 2020. View Article : Google Scholar : PubMed/NCBI

71 

Vaz S, Hadaschik B, Gabriel M, Herrmann K, Eiber M and Costa D: Influence of androgen deprivation therapy on PSMA expression and PSMA-ligand PET imaging of prostate cancer patients. Eur J Nucl Med Mol Imaging. 47:9–15. 2020. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Watanabe R, Sakaue T, Miura N, Kikugawa T and Saika T: Prostate‑specific membrane antigen: Molecular functions and emerging roles as a therapeutic target (Review). Mol Med Rep 33: 122, 2026.
APA
Watanabe, R., Sakaue, T., Miura, N., Kikugawa, T., & Saika, T. (2026). Prostate‑specific membrane antigen: Molecular functions and emerging roles as a therapeutic target (Review). Molecular Medicine Reports, 33, 122. https://doi.org/10.3892/mmr.2026.13832
MLA
Watanabe, R., Sakaue, T., Miura, N., Kikugawa, T., Saika, T."Prostate‑specific membrane antigen: Molecular functions and emerging roles as a therapeutic target (Review)". Molecular Medicine Reports 33.4 (2026): 122.
Chicago
Watanabe, R., Sakaue, T., Miura, N., Kikugawa, T., Saika, T."Prostate‑specific membrane antigen: Molecular functions and emerging roles as a therapeutic target (Review)". Molecular Medicine Reports 33, no. 4 (2026): 122. https://doi.org/10.3892/mmr.2026.13832
Copy and paste a formatted citation
x
Spandidos Publications style
Watanabe R, Sakaue T, Miura N, Kikugawa T and Saika T: Prostate‑specific membrane antigen: Molecular functions and emerging roles as a therapeutic target (Review). Mol Med Rep 33: 122, 2026.
APA
Watanabe, R., Sakaue, T., Miura, N., Kikugawa, T., & Saika, T. (2026). Prostate‑specific membrane antigen: Molecular functions and emerging roles as a therapeutic target (Review). Molecular Medicine Reports, 33, 122. https://doi.org/10.3892/mmr.2026.13832
MLA
Watanabe, R., Sakaue, T., Miura, N., Kikugawa, T., Saika, T."Prostate‑specific membrane antigen: Molecular functions and emerging roles as a therapeutic target (Review)". Molecular Medicine Reports 33.4 (2026): 122.
Chicago
Watanabe, R., Sakaue, T., Miura, N., Kikugawa, T., Saika, T."Prostate‑specific membrane antigen: Molecular functions and emerging roles as a therapeutic target (Review)". Molecular Medicine Reports 33, no. 4 (2026): 122. https://doi.org/10.3892/mmr.2026.13832
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team