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
Oncology Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
May 2012 Volume 3 Issue 5

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
May 2012 Volume 3 Issue 5

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

Antitumor effect of FP3 in a patient-derived tumor tissue xenograft model of gastric carcinoma through an antiangiogenic mechanism

  • Authors:
    • Ketao Jin
    • Huanrong Lan
    • Feilin Cao
    • Zhenzhen Xu
    • Na Han
    • Guangliang Li
    • Kuifeng He
    • Lisong Teng
  • View Affiliations / Copyright

    Affiliations: Department of Surgical Oncology, Taizhou Hospital, Wenzhou Medical College, Linhai, Zhejiang 317000, P.R. China, Department of Gynecology and Obstetrics, Taizhou Hospital, Wenzhou Medical College, Linhai, Zhejiang, P.R. China, Department of Surgical Oncology, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zheijiang, P.R. China, Cancer Chemotherapy Center, Zhejiang Cancer Hospital, Zhejiang University of Chinese Medicine, Hangzhou, Zhejiang 310003, P.R. China
  • Pages: 1052-1058
    |
    Published online on: February 10, 2012
       https://doi.org/10.3892/ol.2012.603
  • 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

FP3 (KH902/KH903) is a novel vascular endothelial growth factor (VEGF) blocker with antiangiogenic properties. Previous studies revealed that FP3, a humanized fusion protein that combines ligand binding elements from the extracellular domains of VEGF receptors 1 and 2 and the Fc portion of IgG1, has an inhibitory effect on the VEGF-mediated proliferation and migration of human umbilical vein endothelial cells, and VEGF-mediated vessel sprouting of rat aortic rings in vitro. Thus, FP3 was considered as a new promising agent in treating human choroidal neovascularization (CNV) caused by age-related macular degeneration (AMD). FP3 also has an antitumor effect in a non-small cell lung cancer cell line (A549) xenograft model in nude mice. However, little is known of the direct effects of FP3 on tumor vessels. In this study, we investigated the effects of FP3 on blood vessels in a patient-derived tumor tissue (PDTT) xenograft model of gastric carcinoma, using large tumors with established vasculature. Treatment with FP3 caused robust and early changes in endothelial cells and pericytes of vessels in the PDTT xenograft model. Vascular density decreased and vascular sprouting was suppressed by treatment with FP3. Pericytes did not degenerate to the same extent as endothelial cells, and those on surviving tumor vessels achieved a more normal phenotype. Our results revealed that FP3 has a direct and rapid antiangiogenic effect on tumor vessels, which was achieved mainly via regression of tumor vasculature, inhibition of new and recurrent vessel growth, and normalization of existing tumor vasculature.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Hanahan D and Weinberg RA: Hallmarks of cancer: the next generation. Cell. 144:646–674. 2011. View Article : Google Scholar : PubMed/NCBI

2 

Paku S and Paweletz N: First steps of tumor-related angiogenesis. Lab Invest. 65:334–346. 1991.PubMed/NCBI

3 

Holash J, Maisonpierre PC, Compton D, Boland P, Alexander CR, Zagzag D, Yancopoulos GD and Wiegand SJ: Vessel cooption, regression, and growth in tumors mediated by angiopoietins and VEGF. Science. 284:1994–1998. 1999. View Article : Google Scholar : PubMed/NCBI

4 

Döme B, Paku S, Somlai B and Tímár J: Vascularization of cutaneous melanoma involves vessel co-option and has clinical significance. J Pathol. 197:355–362. 2002.PubMed/NCBI

5 

Vermeulen PB, Colpaert C, Salgado R, Royers R, Hellemans H, Van Den Heuvel E, Goovaerts G, Dirix LY and Van Marck E: Liver metastases from colorectal adenocarcinomas grow in three patterns with different angiogenesis and desmoplasia. J Pathol. 195:336–342. 2001. View Article : Google Scholar : PubMed/NCBI

6 

Paku S, Kopper L and Nagy P: Development of the vasculature in ‘pushing-type’ liver metastases of an experimental colorectal cancer. Int J Cancer. 115:893–902. 2005.

7 

Kurz H, Burri PH and Djonov VG: Angiogenesis and vascular remodeling by intussusception: from form to function. News Physiol Sci. 18:65–70. 2003.PubMed/NCBI

8 

Osawa M, Masuda M, Kusano K and Fujiwara K: Evidence for a role of platelet endothelial cell adhesion molecule-1 in endothelial cell mechanosignal transduction: is it a mechanoresponsive molecule? J Cell Biol. 158:773–785. 2002. View Article : Google Scholar : PubMed/NCBI

9 

Sundberg C, Nagy JA, Brown LF, Feng D, Eckelhoefer IA, Manseau EJ, Dvorak AM and Dvorak HF: Glomeruloid microvascular proliferation follows adenoviral vascular permeability factor/vascular endothelial growth factor-164 gene delivery. Am J Pathol. 158:1145–1160. 2001. View Article : Google Scholar

10 

Asahara T and Kawamoto A: Endothelial progenitor cells for postnatal vasculogenesis. Am J Physiol Cell Physiol. 287:572–579. 2004. View Article : Google Scholar

11 

Maniotis AJ, Folberg R, Hess A, Seftor EA, Gardner LM, Pe'er J, Trent JM, Meltzer PS and Hendrix MJ: Vascular channel formation by human melanoma cells in vivo and in vitro: vasculogenic mimicry. Am J Pathol. 155:739–752. 1999. View Article : Google Scholar : PubMed/NCBI

12 

Hendrix MJ, Seftor EA, Hess AR and Seftor RE: Vasculogenic mimicry and tumour-cell plasticity: lessons from melanoma. Nat Rev Cancer. 3:411–421. 2003. View Article : Google Scholar : PubMed/NCBI

13 

Ferrara N: Vascular endothelial growth factor: basic science and clinical progress. Endocr Rev. 25:581–611. 2004. View Article : Google Scholar : PubMed/NCBI

14 

Hicklin DJ and Ellis LM: Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol. 23:1011–1027. 2005. View Article : Google Scholar : PubMed/NCBI

15 

Ferrara N, Gerber HP and LeCouter J: The biology of VEGF and its receptors. Nat Med. 9:669–676. 2003. View Article : Google Scholar : PubMed/NCBI

16 

Teng LS, Jin KT, He KF, Wang HH, Cao J and Yu DC: Advances in combination of antiangiogenic agents targeting VEGF-binding and conventional chemotherapy and radiation for cancer treatment. J Chin Med Assoc. 73:281–288. 2010. View Article : Google Scholar : PubMed/NCBI

17 

Teng LS, Jin KT, He KF, Zhang J, Wang HH and Cao J: Clinical applications of VEGF-trap (aflibercept) in cancer treatment. J Chin Med Assoc. 73:449–456. 2010. View Article : Google Scholar : PubMed/NCBI

18 

Jin K, He K, Teng F, Li G, Wang H, Han N, Xu Z, Cao J, Wu J, Yu D and Teng L: FP3: a novel VEGF blocker with antiangiogenic effects in vitro and antitumour effects in vivo. Clin Transl Oncol. 13:878–884. 2011. View Article : Google Scholar : PubMed/NCBI

19 

Zhang M, Zhang J, Yan M, Li H, Yang C and Yu D: Recombinant anti-vascular endothelial growth factor fusion protein efficiently suppresses choridal neovasularization in monkeys. Mol Vis. 14:37–49. 2008.

20 

Zhang M, Yu D, Yang C, Xia Q, Li W, Liu B and Li H: The pharmacology study of a new recombinant human VEGF receptor-fc fusion protein on experimental choroidal neovascularization. Pharm Res. 26:204–210. 2009. View Article : Google Scholar : PubMed/NCBI

21 

Zhang M, Zhang J, Yan M, Luo D, Zhu W, Kaiser PK and Yu DC; KH902 Phase 1 Study Group. A phase 1 study of KH902, a vascular endothelial growth factor receptor decoy, for exudative age-related macular degeneration. Ophthalmology. 118:672–678. 2011. View Article : Google Scholar : PubMed/NCBI

22 

Inai T, Mancuso M, Hashizume H, Baffert F, Haskell A, Baluk P, Hu-Lowe DD, Shalinsky DR, Thurston G, Yancopoulos GD and McDonald DM: Inhibition of vascular endothelial growth factor (VEGF) signaling in cancer causes loss of endothelial fenestrations, regression of tumor vessels, and appearance of basement membrane ghosts. Am J Pathol. 165:35–52. 2004. View Article : Google Scholar

23 

Jin K, Teng L, Shen Y, He K, Xu Z and Li G: Patient-derived human tumour tissue xenografts in immunodeficient mice: a systematic review. Clin Transl Oncol. 12:473–480. 2010. View Article : Google Scholar : PubMed/NCBI

24 

Jin K, He K, Li G and Teng L: Personalized cancer therapy using a patient-derived tumor tissue xenograft model: a translational field worthy of exploring further? Pers Med. 7:597–606. 2010. View Article : Google Scholar

25 

Jin K, He K, Teng F, Han N, Li G, Xu Z and Teng L: Heterogeneity in primary tumors and corresponding metastases: could it provide us with any hints to personalize cancer therapy? Pers Med. 8:175–182. 2011. View Article : Google Scholar

26 

Jin K, He K, Han N, Li G, Wang H, Xu Z, Jiang H, Zhang J and Teng L: Establishment of a PDTT xenograft model of gastric carcinoma and its application in personalized therapeutic regimen selection. Hepatogastroenterology. 58:1814–1822. 2011.PubMed/NCBI

27 

Mancuso MR, Davis R, Norberg SM, O'Brien S, Sennino B, Nakahara T, Yao VJ, Inai T, Brooks P, Freimark B, Shalinsky DR, Hu-Lowe DD and McDonald DM: Rapid vascular regrowth in tumors after reversal of VEGF inhibition. J Clin Invest. 116:2610–2621. 2006. View Article : Google Scholar : PubMed/NCBI

28 

Morikawa S, Baluk P, Kaidoh T, Haskell A, Jain RK and McDonald DM: Abnormalities in pericytes on blood vessels and endothelial sprouts in tumors. Am J Pathol. 160:985–1000. 2002. View Article : Google Scholar : PubMed/NCBI

29 

Baluk P, Morikawa S, Haskell A, Mancuso M and McDonald DM: Abnormalities of basement membrane on blood vessels and endothelial sprouts in tumors. Am J Pathol. 163:1801–1815. 2003. View Article : Google Scholar : PubMed/NCBI

30 

Willett CG, Boucher Y, Di Tomaso E, Duda DG, Munn LL, Tong RT, Chung DC, Sahani DV, Kalva SP, Kozin SV, et al: Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer. Nat Med. 10:145–147. 2004. View Article : Google Scholar

31 

Baffert F, Le T, Sennino B, Thurston G, Kuo CJ, Hu-Lowe D and McDonald DM: Cellular changes in normal blood capillaries undergoing regression after inhibition of VEGF signaling. Am J Physiol Heart Circ Physiol. 290:H547–559. 2006. View Article : Google Scholar : PubMed/NCBI

32 

Byrne AT, Ross L, Holash J, Nakanishi M, Hu L, Hofmann JI, Yancopoulos GD and Jaffe RB: Vascular endothelial growth factor-trap decreases tumor burden, inhibits ascites, and causes dramatic vascular remodeling in an ovarian cancer model. Clin Cancer Res. 9:5721–5728. 2003.

33 

Jain RK: Normalizing tumor vasculature with anti-angiogenic therapy: a new paradigm for combination therapy. Nat Med. 7:987–989. 2001. View Article : Google Scholar : PubMed/NCBI

34 

Jain RK: Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science. 307:58–62. 2005. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Jin K, Lan H, Cao F, Xu Z, Han N, Li G, He K and Teng L: Antitumor effect of FP3 in a patient-derived tumor tissue xenograft model of gastric carcinoma through an antiangiogenic mechanism. Oncol Lett 3: 1052-1058, 2012.
APA
Jin, K., Lan, H., Cao, F., Xu, Z., Han, N., Li, G. ... Teng, L. (2012). Antitumor effect of FP3 in a patient-derived tumor tissue xenograft model of gastric carcinoma through an antiangiogenic mechanism. Oncology Letters, 3, 1052-1058. https://doi.org/10.3892/ol.2012.603
MLA
Jin, K., Lan, H., Cao, F., Xu, Z., Han, N., Li, G., He, K., Teng, L."Antitumor effect of FP3 in a patient-derived tumor tissue xenograft model of gastric carcinoma through an antiangiogenic mechanism". Oncology Letters 3.5 (2012): 1052-1058.
Chicago
Jin, K., Lan, H., Cao, F., Xu, Z., Han, N., Li, G., He, K., Teng, L."Antitumor effect of FP3 in a patient-derived tumor tissue xenograft model of gastric carcinoma through an antiangiogenic mechanism". Oncology Letters 3, no. 5 (2012): 1052-1058. https://doi.org/10.3892/ol.2012.603
Copy and paste a formatted citation
x
Spandidos Publications style
Jin K, Lan H, Cao F, Xu Z, Han N, Li G, He K and Teng L: Antitumor effect of FP3 in a patient-derived tumor tissue xenograft model of gastric carcinoma through an antiangiogenic mechanism. Oncol Lett 3: 1052-1058, 2012.
APA
Jin, K., Lan, H., Cao, F., Xu, Z., Han, N., Li, G. ... Teng, L. (2012). Antitumor effect of FP3 in a patient-derived tumor tissue xenograft model of gastric carcinoma through an antiangiogenic mechanism. Oncology Letters, 3, 1052-1058. https://doi.org/10.3892/ol.2012.603
MLA
Jin, K., Lan, H., Cao, F., Xu, Z., Han, N., Li, G., He, K., Teng, L."Antitumor effect of FP3 in a patient-derived tumor tissue xenograft model of gastric carcinoma through an antiangiogenic mechanism". Oncology Letters 3.5 (2012): 1052-1058.
Chicago
Jin, K., Lan, H., Cao, F., Xu, Z., Han, N., Li, G., He, K., Teng, L."Antitumor effect of FP3 in a patient-derived tumor tissue xenograft model of gastric carcinoma through an antiangiogenic mechanism". Oncology Letters 3, no. 5 (2012): 1052-1058. https://doi.org/10.3892/ol.2012.603
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