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 and Clinical Oncology
Join Editorial Board Propose a Special Issue
Print ISSN: 2049-9450 Online ISSN: 2049-9469
Journal Cover
September-2022 Volume 17 Issue 3

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
September-2022 Volume 17 Issue 3

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
Article Open Access

Nafamostat mesylate prevents metastasis and dissemination of neuroblastoma through vascular endothelial growth factor inhibition

  • Authors:
    • Mari Morimoto
    • Hidemi Toyoda
    • Kaori Niwa
    • Ryo Hanaki
    • Taro Okuda
    • Daisuke Nakato
    • Keishiro Amano
    • Shotaro Iwamoto
    • Masahiro Hirayama
  • View Affiliations / Copyright

    Affiliations: Department of Pediatrics, Mie University Graduate School of Medicine, Tsu, Mie 514‑8507, Japan
    Copyright: © Morimoto et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 138
    |
    Published online on: July 21, 2022
       https://doi.org/10.3892/mco.2022.2571
  • 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

Neuroblastoma is a highly malignant disease with a poor prognosis and few treatment options. Despite conventional chemotherapy for neuroblastoma, resistance, invasiveness, and metastatic mobility limit the treatment efficacy. Therefore, it is necessary to develop new strategies for treating neuroblastoma. The present study aimed to evaluate the anticancer effects of nafamostat mesylate, a previously known serine protease inhibitor, on neuroblastoma cells. Effects of nafamostat mesylate on neuroblastoma cell migration and proliferation were analyzed by wound healing assay and WST‑8 assay, respectively. To elucidate the mechanisms underlying the effects of nafamostat mesylate on neuroblastoma, the expression levels of NF‑κB were measured via western blotting, and the production of the cytokine vascular endothelial growth factor (VEGF) in the cell culture supernatants was determined via ELISA. In addition, a mouse model of hematogenous metastasis was used to investigate the effects of nafamostat mesylate on neuroblastoma. It was determined that nafamostat mesylate significantly inhibited migration and invasion of Neuro‑2a cells, but it had no effect on cell proliferation at 24 h after treatment. Exposure of Neuro‑2a cells to nafamostat mesylate resulted in decreased vascular endothelial growth factor production, which could be a pivotal mechanism underlying the inhibitory effects of neuroblastoma metastasis. The results of the present study suggest that nafamostat mesylate may be an effective treatment against neuroblastoma invasion and metastasis.
View Figures

Figure 1

Figure 2

Figure 3

View References

1 

Matthay KK, Maris JM, Schleiermacher G, Nakagawara A, Mackall CL, Diller L and Weiss WA: Neuroblastoma. Nat Rev Dis Primers. 2(16078)2016.PubMed/NCBI View Article : Google Scholar

2 

Shankar V, Hori H, Kihira K, Lei Q, Toyoda H, Iwamoto S and Komada Y: Mesenchymal stromal cell secretome up-regulates 47 kDa CXCR4 expression, and induce invasiveness in neuroblastoma cell lines. PLoS One. 10(e0120069)2015.PubMed/NCBI View Article : Google Scholar

3 

Matthay KK: Chemotherapy for neuroblastoma: Does it hit the target? Lancet Oncol. 9:195–196. 2008.PubMed/NCBI View Article : Google Scholar

4 

Guan X: Cancer metastases: Challenges and opportunities. Acta Pharm Sin B. 5:402–418. 2015.PubMed/NCBI View Article : Google Scholar

5 

Joyce JA and Pollard JW: Microenvironmental regulation of metastasis. Nat Rev Cancer. 9:239–252. 2009.PubMed/NCBI View Article : Google Scholar

6 

Carmeliet P and Jain RK: Molecular mechanisms and clinical applications of angiogenesis. Nature. 473:298–307. 2011.PubMed/NCBI View Article : Google Scholar

7 

Iwashita K, Kitamura K, Narikiyo T, Adachi M, Shiraishi N, Miyoshi T, Nagano J, Tuyen DG, Nonoguchi H and Tomita K: Inhibition of prostasin secretion by serine protease inhibitors in the kidney. J Am Soc Nephrol. 14:11–16. 2003.PubMed/NCBI View Article : Google Scholar

8 

Fujiwara Y, Furukawa K, Haruki K, Shimada Y, Iida T, Shiba H, Uwagawa T, Ohashi T and Yanaga K: Nafamostat mesilate can prevent adhesion, invasion and peritoneal dissemination of pancreatic cancer thorough nuclear factor kappa-B inhibition. J Hepatobiliary Pancreat Sci. 18:731–739. 2011.PubMed/NCBI View Article : Google Scholar

9 

Kimura T, Fuchimoto S, Iwagaki H, Hizuta A and Orita K: Inhibitory effect of nafamostat mesilate on metastasis into the livers of mice and on invasion of the extracellular matrix by cancer cells. J Int Med Res. 20:343–352. 1992.PubMed/NCBI View Article : Google Scholar

10 

Lu YX, Ju HQ, Wang F, Chen LZ, Wu QN, Sheng H, Mo HY, Pan ZZ, Xie D, Kang TB, et al: Inhibition of the NF-κB pathway by nafamostat mesilate suppresses colorectal cancer growth and metastasis. Cancer Lett. 380:87–97. 2016.PubMed/NCBI View Article : Google Scholar

11 

Mander S, You DJ, Park S, Kim DH, Yong HJ, Kim DS, Ahn C, Kim YH, Seong JY and Hwang JI: Nafamostat mesilate negatively regulates the metastasis of triple-negative breast cancer cells. Arch Pharm Res. 41:229–242. 2018.PubMed/NCBI View Article : Google Scholar

12 

Saito N, Uwagawa T, Hamura R, Takada N, Sugano H, Shirai Y, Shiba H, Ohashi T and Yanaga K: Prevention of early liver metastasis after pancreatectomy by perioperative administration of a nuclear factor-κB inhibitor in mice. Surgery. 166:991–996. 2019.PubMed/NCBI View Article : Google Scholar

13 

Uwagawa T, Misawa T, Tsutsui N, Ito R, Gocho T, Hirohara S, Sadaoka S and Yanaga K: Phase II study of gemcitabine in combination with regional arterial infusion of nafamostat mesilate for advanced pancreatic cancer. Am J Clin Oncol. 36:44–48. 2013.PubMed/NCBI View Article : Google Scholar

14 

Yamashita Y, Ishiguro Y, Sano D, Kimura M, Fujita K, Yoshida T, Horiuchi C, Taguchi T, Matsuda H, Mikami Y and Tsukuda M: Antitumor effects of Nafamostat mesilate on head and neck squamous cell carcinoma. Auris Nasus Larynx. 34:487–491. 2007.PubMed/NCBI View Article : Google Scholar

15 

Shan D, Chen L, Njardarson JT, Gaul C, Ma X, Danishefsky SJ and Huang XY: Synthetic analogues of migrastatin that inhibit mammary tumor metastasis in mice. Proc Natl Acad Sci USA. 102:3772–3776. 2005.PubMed/NCBI View Article : Google Scholar

16 

Qi L, Toyoda H, Shankar V, Sakurai N, Amano K, Kihira K, Iwasa T, Deguchi T, Hori H, Azuma E, et al: Heterogeneity of neuroblastoma cell lines in insulin-like growth factor 1 receptor/Akt pathway-mediated cell proliferative responses. Cancer Sci. 104:1162–1171. 2013.PubMed/NCBI View Article : Google Scholar

17 

Toyoda H, Wimmer E and Cello J: Oncolytic poliovirus therapy and immunization with poliovirus-infected cell lysate induces potent antitumor immunity against neuroblastoma in vivo. Int J Oncol. 38:81–87. 2011.PubMed/NCBI

18 

Yu JL, Chan S, Fung MK and Chan GC: Mesenchymal stem cells accelerated growth and metastasis of neuroblastoma and preferentially homed towards both primary and metastatic loci in orthotopic neuroblastoma model. BMC Cancer. 21(393)2021.PubMed/NCBI View Article : Google Scholar

19 

Toyoda H, Ido M, Hayashi T, Gabazza EC, Suzuki K, Kisenge RR, Kang J, Hori H and Komada Y: Experimental treatment of human neuroblastoma using live-attenuated poliovirus. Int J Oncol. 24:49–58. 2004.PubMed/NCBI

20 

Kitchen P, Salman MM, Halsey AM, Clarke-Bland C, MacDonald JA, Ishida H, Vogel HJ, Almutiri S, Logan A, Kreida S, et al: Targeting aquaporin-4 subcellular localization to treat central nervous system edema. Cell. 181:784–799.e19. 2020.PubMed/NCBI View Article : Google Scholar

21 

Sylvain NJ, Salman MM, Pushie MJ, Hou H, Meher V, Herlo R, Peeling L and Kelly ME: The effects of trifluoperazine on brain edema, aquaporin-4 expression and metabolic markers during the acute phase of stroke using photothrombotic mouse model. Biochim Biophys Acta Biomembr. 1863(183573)2021.PubMed/NCBI View Article : Google Scholar

22 

Markou A, Unger L, Abir-Awan M, Saadallah A, Halsey A, Balklava Z, Conner M, Törnroth-Horsefield S, Greenhill SD, Conner A, et al: Molecular mechanisms governing aquaporin relocalisation. Biochim Biophys Acta Biomembr. 1864(183853)2022.PubMed/NCBI View Article : Google Scholar

23 

Salman MM, Kitchen P, Yool AJ and Bill RM: Recent breakthroughs and future directions in drugging aquaporins. Trends Pharmacol Sci. 43:30–42. 2022.PubMed/NCBI View Article : Google Scholar

24 

Wagner K, Unger L, Salman MM, Kitchen P, Bill RM and Yool AJ: Signaling mechanisms and pharmacological modulators governing diverse aquaporin functions in human health and disease. Int J Mol Sci. 23(1388)2022.PubMed/NCBI View Article : Google Scholar

25 

Cao X, Geradts J, Dewhirst MW and Lo HW: Upregulation of VEGF-A and CD24 gene expression by the tGLI1 transcription factor contributes to the aggressive behavior of breast cancer cells. Oncogene. 31:104–115. 2012.PubMed/NCBI View Article : Google Scholar

26 

Fallah J and Rini BI: HIF Inhibitors: Status of current clinical development. Curr Oncol Rep. 21(6)2019.PubMed/NCBI View Article : Google Scholar

27 

Su F, Geng J, Li X, Qiao C, Luo L, Feng J, Dong X and Lv M: SP1 promotes tumor angiogenesis and invasion by activating VEGF expression in an acquired trastuzumab-resistant ovarian cancer model. Oncol Rep. 38:2677–2684. 2017.PubMed/NCBI View Article : Google Scholar

28 

Wei D, Le X, Zheng L, Wang L, Frey JA, Gao AC, Peng Z, Huang S, Xiong HQ, Abbruzzese JL and Xie K: Stat3 activation regulates the expression of vascular endothelial growth factor and human pancreatic cancer angiogenesis and metastasis. Oncogene. 22:319–329. 2003.PubMed/NCBI View Article : Google Scholar

29 

Raimondi I, Izzo L, Tunesi M, Comar M, Albani D and Giordano C: Organ-On-A-Chip in vitro models of the brain and the blood-brain barrier and their value to study the microbiota-gut-brain axis in neurodegeneration. Front Bioeng Biotechnol. 7(435)2020.PubMed/NCBI View Article : Google Scholar

30 

Salman MM, Marsh G, Kusters I, Delince M, Di Caprio G, Upadhyayula S, de Nola G, Hunt R, Ohashi KG, Gray T, et al: Design and validation of a human brain endothelial microvessel-on-a-chip open microfluidic model enabling advanced optical imaging. Front Bioeng Biotechnol. 8(573775)2020.PubMed/NCBI View Article : Google Scholar

31 

Aldewachi H, Al-Zidan RN, Conner MT and Salman MM: High-Throughput screening platforms in the discovery of novel drugs for neurodegenerative diseases. Bioengineering (Basel). 8(30)2021.PubMed/NCBI View Article : Google Scholar

32 

Salman MM, Al-Obaidi Z, Kitchen P, Loreto A, Bill RM and Wade-Martins R: Advances in applying computer-aided drug design for neurodegenerative diseases. Int J Mol Sci. 22(4688)2021.PubMed/NCBI View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Morimoto M, Toyoda H, Niwa K, Hanaki R, Okuda T, Nakato D, Amano K, Iwamoto S and Hirayama M: Nafamostat mesylate prevents metastasis and dissemination of neuroblastoma through vascular endothelial growth factor inhibition. Mol Clin Oncol 17: 138, 2022.
APA
Morimoto, M., Toyoda, H., Niwa, K., Hanaki, R., Okuda, T., Nakato, D. ... Hirayama, M. (2022). Nafamostat mesylate prevents metastasis and dissemination of neuroblastoma through vascular endothelial growth factor inhibition. Molecular and Clinical Oncology, 17, 138. https://doi.org/10.3892/mco.2022.2571
MLA
Morimoto, M., Toyoda, H., Niwa, K., Hanaki, R., Okuda, T., Nakato, D., Amano, K., Iwamoto, S., Hirayama, M."Nafamostat mesylate prevents metastasis and dissemination of neuroblastoma through vascular endothelial growth factor inhibition". Molecular and Clinical Oncology 17.3 (2022): 138.
Chicago
Morimoto, M., Toyoda, H., Niwa, K., Hanaki, R., Okuda, T., Nakato, D., Amano, K., Iwamoto, S., Hirayama, M."Nafamostat mesylate prevents metastasis and dissemination of neuroblastoma through vascular endothelial growth factor inhibition". Molecular and Clinical Oncology 17, no. 3 (2022): 138. https://doi.org/10.3892/mco.2022.2571
Copy and paste a formatted citation
x
Spandidos Publications style
Morimoto M, Toyoda H, Niwa K, Hanaki R, Okuda T, Nakato D, Amano K, Iwamoto S and Hirayama M: Nafamostat mesylate prevents metastasis and dissemination of neuroblastoma through vascular endothelial growth factor inhibition. Mol Clin Oncol 17: 138, 2022.
APA
Morimoto, M., Toyoda, H., Niwa, K., Hanaki, R., Okuda, T., Nakato, D. ... Hirayama, M. (2022). Nafamostat mesylate prevents metastasis and dissemination of neuroblastoma through vascular endothelial growth factor inhibition. Molecular and Clinical Oncology, 17, 138. https://doi.org/10.3892/mco.2022.2571
MLA
Morimoto, M., Toyoda, H., Niwa, K., Hanaki, R., Okuda, T., Nakato, D., Amano, K., Iwamoto, S., Hirayama, M."Nafamostat mesylate prevents metastasis and dissemination of neuroblastoma through vascular endothelial growth factor inhibition". Molecular and Clinical Oncology 17.3 (2022): 138.
Chicago
Morimoto, M., Toyoda, H., Niwa, K., Hanaki, R., Okuda, T., Nakato, D., Amano, K., Iwamoto, S., Hirayama, M."Nafamostat mesylate prevents metastasis and dissemination of neuroblastoma through vascular endothelial growth factor inhibition". Molecular and Clinical Oncology 17, no. 3 (2022): 138. https://doi.org/10.3892/mco.2022.2571
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