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-2015 Volume 11 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-2015 Volume 11 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
Article Open Access

Platelets are associated with xenograft tumor growth and the clinical malignancy of ovarian cancer through an angiogenesis-dependent mechanism

  • Authors:
    • Lei Yuan
    • Xishi Liu
  • View Affiliations / Copyright

    Affiliations: Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, P.R. China
    Copyright: © Yuan et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 2449-2458
    |
    Published online on: December 11, 2014
       https://doi.org/10.3892/mmr.2014.3082
  • 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

Platelets are known to facilitate tumor metastasis and thrombocytosis has been associated with an adverse prognosis in ovarian cancer. However, the role of platelets in primary tumour growth remains to be elucidated. The present study demonstrated that the expression levels of various markers in platelets, endothelial adherence and angiogenesis, including, platelet glycoprotein IIb (CD41), platelet endothelial cell adhesion molecule 1 (CD31), vascular endothelial growth factor (VEGF), lysyl oxidase, focal adhesion kinase and breast cancer anti‑estrogen resistance 1, were expressed at higher levels in patients with malignant carcinoma, compared with those with borderline cystadenoma and cystadenoma. In addition, the endothelial markers CD31 and VEGF were found to colocalize with the platelet marker CD41 in the malignant samples. Since mice transplanted with human ovarian cancer cells (SKOV3) demonstrated elevated tumor size and decreased survival rate when treated with thrombin or thrombopoietin (TPO), the platelets appeared to promote primary tumor growth. Depleting platelets using antibodies or by pretreating the cancer cells with hirudin significantly attenuated the transplanted tumor growth. The platelets contributed to late, but not early stages of tumor proliferation, as mice treated with platelet‑depleting antibody 1 day prior to and 11 days after tumor transplantation had the same tumor volumes. By contrast, tumor size in the early TPO‑injected group was increased significantly compared with the late TPO‑injected group. These findings suggested that the interplay between platelets and angiogenesis may contribute to ovarian cancer growth. Therefore, platelets and their associated signaling and adhesive molecules may represent potential therapeutic targets for ovarian cancer.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8

View References

1 

Felding-Habermann B, Habermann R, Saldivar E and Ruggeri ZM: Role of beta3 integrins in melanoma cell adhesion to activated platelets under flow. J Biol Chem. 271:5892–5900. 1996. View Article : Google Scholar : PubMed/NCBI

2 

Borsig L, Wong R, Feramisco J, et al: Heparin and cancer revisited: mechanistic connections involving platelets, P-selectin, carcinoma mucins, and tumor metastasis. Proc Natl Acad Sci USA. 98:3352–3357. 2001. View Article : Google Scholar : PubMed/NCBI

3 

Labelle M, Begum S and Hynes RO: Direct signaling between platelets and cancer cells induces an epithelial-mesenchymal-like transition and promotes metastasis. Cancer Cell. 20:576–590. 2011. View Article : Google Scholar : PubMed/NCBI

4 

Buergy D, Wenz F, Groden C and Brockmann MA: Tumor-platelet interaction in solid tumors. Int J Cancer. 130:2747–2760. 2012. View Article : Google Scholar : PubMed/NCBI

5 

Rao AK and Rao DA: Platelets signal and tumors take off. Blood. 120:4667–4668. 2012. View Article : Google Scholar : PubMed/NCBI

6 

Douglas VK, Tallman MS, Cripe LD and Peterson LC: Thrombopoietin administered during induction chemotherapy to patients with acute myeloid leukemia induces transient morphologic changes that may resemble chronic myeloproliferative disorders. Am J Clin Path. 117:844–850. 2002. View Article : Google Scholar : PubMed/NCBI

7 

Stone RL, Nick AM, McNeish IA, et al: Paraneoplastic thrombocytosis in ovarian cancer. N Engl J Med. 366:610–618. 2012. View Article : Google Scholar : PubMed/NCBI

8 

Wang-Tilz Y, Tilz C, Wang B, Tilz GP and Stefan H: Influence of lamotrigine and topiramate on MDR1 expression in difficult-to-treat temporal lobe epilepsy. Epilepsia. 47:233–239. 2006. View Article : Google Scholar : PubMed/NCBI

9 

Ma S, Liu X, Geng JG and Guo SW: Increased SLIT immunoreactivity as a biomarker for recurrence in endometrial carcinoma. Am J Obstet Gynecol. 202:68e61–e68. e112010. View Article : Google Scholar

10 

Feng W, Madajka M, Kerr BA, et al: A novel role for platelet secretion in angiogenesis: mediating bone marrow-derived cell mobilization and homing. Blood. 117:3893–3902. 2011. View Article : Google Scholar : PubMed/NCBI

11 

Manetta A, Satyaswaroop PG, Hamilton T, et al: Radio imaging of human ovarian carcinoma xenograft in nude mice. Gynecol Oncol. 28:292–299. 1987. View Article : Google Scholar : PubMed/NCBI

12 

Holmes CE, Levis JE and Ornstein DL: Activated platelets enhance ovarian cancer cell invasion in a cellular model of metastasis. Clin Exp Metastasis. 26:653–661. 2009. View Article : Google Scholar : PubMed/NCBI

13 

Trikha M, Zhou Z, Timar J, et al: Multiple roles for platelet GPIIb/IIIa and alphavbeta3 integrins in tumor growth, angiogenesis, and metastasis. Cancer Res. 62:2824–2833. 2002.PubMed/NCBI

14 

Dardik R, Savion N, Kaufmann Y and Varon D: Thrombin promotes platelet-mediated melanoma cell adhesion to endothelial cells under flow conditions: role of platelet glycoproteins P-selectin and GPIIb-IIIA. Br J Cancer. 77:2069–2075. 1998. View Article : Google Scholar : PubMed/NCBI

15 

Matsui H, Harada I and Sawada Y: Src, p130Cas, and Mechanotransduction in Cancer Cells. Genes Cancer. 3:394–401. 2012. View Article : Google Scholar : PubMed/NCBI

16 

Nick AM, Stone RL, Armaiz-Pena G, et al: Silencing of p130cas in ovarian carcinoma: a novel mechanism for tumor cell death. J Natl Cancer Inst. 103:1596–1612. 2011. View Article : Google Scholar : PubMed/NCBI

17 

Sawada Y, Tamada M, Dubin-Thaler BJ, et al: Force sensing by mechanical extension of the Src family kinase substrate p130Cas. Cell. 127:1015–1026. 2006. View Article : Google Scholar : PubMed/NCBI

18 

Zhang P, Guo A, Possemato A, et al: Identification and functional characterization of p130Cas as a substrate of protein tyrosine phosphatase nonreceptor 14. Oncogene. 32:2087–2095. 2013. View Article : Google Scholar :

19 

Chatzizacharias NA, Kouraklis GP and Theocharis SE: Clinical significance of FAK expression in human neoplasia. Histol Histopathol. 23:629–650. 2008.PubMed/NCBI

20 

Goel HL and Mercurio AM: VEGF targets the tumour cell. Nat Rev Cancer. 13:871–882. 2013. View Article : Google Scholar : PubMed/NCBI

21 

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

22 

Prow D and Vadhan-Raj S: Thrombopoietin: biology and potential clinical applications. Oncology (Williston Park). 12:1597–1604. 1607–1598; discussion 1611–1594. 1998.

23 

Dardik R, Kaufmann Y, Savion N, et al: Platelets mediate tumor cell adhesion to the subendothelium under flow conditions: involvement of platelet GPIIb-IIIa and tumor cell alpha(v) integrins. Int J Cancer. 70:201–207. 1997. View Article : Google Scholar : PubMed/NCBI

24 

Konstantopoulos K and Thomas SN: Cancer cells in transit: the vascular interactions of tumor cells. Annu Rev Biomed Eng. 11:177–202. 2009. View Article : Google Scholar : PubMed/NCBI

25 

McCarty OJ, Mousa SA, Bray PF and Konstantopoulos K: Immobilized platelets support human colon carcinoma cell tethering, rolling, and firm adhesion under dynamic flow conditions. Blood. 96:1789–1797. 2000.PubMed/NCBI

26 

Ay C, Dunkler D, Pirker R, et al: High D-dimer levels are associated with poor prognosis in cancer patients. Haematologica. 97:1158–1164. 2012. View Article : Google Scholar : PubMed/NCBI

27 

Dirix LY, Salgado R, Weytjens R, et al: Plasma fibrin D-dimer levels correlate with tumour volume, progression rate and survival in patients with metastatic breast cancer. Br J Cancer. 86:389–395. 2002. View Article : Google Scholar : PubMed/NCBI

28 

Zigler M, Kamiya T, Brantley EC, Villares GJ and Bar-Eli M: PAR-1 and thrombin: the ties that bind the microenvironment to melanoma metastasis. Cancer Res. 71:6561–6566. 2011. View Article : Google Scholar : PubMed/NCBI

29 

Cowell LN, Graham JD, Bouton AH, Clarke CL and O’Neill GM: Tamoxifen treatment promotes phosphorylation of the adhesion molecules, p130Cas/BCAR1, FAK and Src, via an adhesion-dependent pathway. Oncogene. 25:7597–7607. 2006. View Article : Google Scholar : PubMed/NCBI

30 

McLean GW, Carragher NO, Avizienyte E, et al: The role of focal-adhesion kinase in cancer - a new therapeutic opportunity. Nat Rev Cancer. 5:505–515. 2005. View Article : Google Scholar : PubMed/NCBI

31 

Ward KK, Tancioni I, Lawson C, et al: Inhibition of focal adhesion kinase (FAK) activity prevents anchorage-independent ovarian carcinoma cell growth and tumor progression. Clin Exp Metastasis. 30:579–594. 2013. View Article : Google Scholar : PubMed/NCBI

32 

Chen XL, Nam JO, Jean C, et al: VEGF-induced vascular permeability is mediated by FAK. Dev Cell. 22:146–157. 2012. View Article : Google Scholar : PubMed/NCBI

33 

Erler JT, Bennewith KL, Nicolau M, et al: Lysyl oxidase is essential for hypoxia-induced metastasis. Nature. 440:1222–1226. 2006. View Article : Google Scholar : PubMed/NCBI

34 

Kirschmann DA, Seftor EA, Fong SF, et al: A molecular role for lysyl oxidase in breast cancer invasion. Cancer Res. 62:4478–4483. 2002.PubMed/NCBI

35 

Baker AM, Bird D, Lang G, Cox TR and Erler JT: Lysyl oxidase enzymatic function increases stiffness to drive colorectal cancer progression through FAK. Oncogene. 32:1863–1868. 2013. View Article : Google Scholar

36 

Baker AM, Cox TR, Bird D, et al: The role of lysyl oxidase in SRC-dependent proliferation and metastasis of colorectal cancer. J Natl Cancer Inst. 103:407–424. 2011. View Article : Google Scholar : PubMed/NCBI

37 

Lapointe J, Li C, Higgins JP, et al: Gene expression profiling identifies clinically relevant subtypes of prostate cancer. Proc Natl Acad Sci USA. 101:811–816. 2004. View Article : Google Scholar : PubMed/NCBI

38 

Battegay EJ, Rupp J, Iruela-Arispe L, Sage EH and Pech M: PDGF-BB modulates endothelial proliferation and angiogenesis in vitro via PDGF beta-receptors. J Cell Biol. 125:917–928. 1994. View Article : Google Scholar : PubMed/NCBI

39 

Anglesio MS, George J, Kulbe H, et al: IL6-STAT3-HIF signaling and therapeutic response to the angiogenesis inhibitor sunitinib in ovarian clear cell cancer. Clin Cancer Res. 17:2538–2548. 2011. View Article : Google Scholar : PubMed/NCBI

40 

Harker LA, Marzec UM, Kelly AB, et al: Prevention of thrombocytopenia and neutropenia in a nonhuman primate model of marrow suppressive chemotherapy by combining pegylated recombinant human megakaryocyte growth and development factor and recombinant human granulocyte colony-stimulating factor. Blood. 89:155–165. 1997.PubMed/NCBI

41 

Grossmann A, Lenox J, Ren HP, et al: Thrombopoietin accelerates platelet, red blood cell, and neutrophil recovery in myelosuppressed mice. Exp Hematol. 24:1238–1246. 1996.PubMed/NCBI

42 

Bergmeier W, Piffath CL, Goerge T, et al: The role of platelet adhesion receptor GPIbalpha far exceeds that of its main ligand, von Willebrand factor, in arterial thrombosis. Proc Natl Acad Sci USA. 103:16900–16905. 2006. View Article : Google Scholar : PubMed/NCBI

43 

Cho MS, Bottsford-Miller J, Vasquez HG, et al: Platelets increase the proliferation of ovarian cancer cells. Blood. 120:4869–4872. 2012. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Yuan L and Liu X: Platelets are associated with xenograft tumor growth and the clinical malignancy of ovarian cancer through an angiogenesis-dependent mechanism. Mol Med Rep 11: 2449-2458, 2015.
APA
Yuan, L., & Liu, X. (2015). Platelets are associated with xenograft tumor growth and the clinical malignancy of ovarian cancer through an angiogenesis-dependent mechanism. Molecular Medicine Reports, 11, 2449-2458. https://doi.org/10.3892/mmr.2014.3082
MLA
Yuan, L., Liu, X."Platelets are associated with xenograft tumor growth and the clinical malignancy of ovarian cancer through an angiogenesis-dependent mechanism". Molecular Medicine Reports 11.4 (2015): 2449-2458.
Chicago
Yuan, L., Liu, X."Platelets are associated with xenograft tumor growth and the clinical malignancy of ovarian cancer through an angiogenesis-dependent mechanism". Molecular Medicine Reports 11, no. 4 (2015): 2449-2458. https://doi.org/10.3892/mmr.2014.3082
Copy and paste a formatted citation
x
Spandidos Publications style
Yuan L and Liu X: Platelets are associated with xenograft tumor growth and the clinical malignancy of ovarian cancer through an angiogenesis-dependent mechanism. Mol Med Rep 11: 2449-2458, 2015.
APA
Yuan, L., & Liu, X. (2015). Platelets are associated with xenograft tumor growth and the clinical malignancy of ovarian cancer through an angiogenesis-dependent mechanism. Molecular Medicine Reports, 11, 2449-2458. https://doi.org/10.3892/mmr.2014.3082
MLA
Yuan, L., Liu, X."Platelets are associated with xenograft tumor growth and the clinical malignancy of ovarian cancer through an angiogenesis-dependent mechanism". Molecular Medicine Reports 11.4 (2015): 2449-2458.
Chicago
Yuan, L., Liu, X."Platelets are associated with xenograft tumor growth and the clinical malignancy of ovarian cancer through an angiogenesis-dependent mechanism". Molecular Medicine Reports 11, no. 4 (2015): 2449-2458. https://doi.org/10.3892/mmr.2014.3082
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