Vascular endothelial growth factor (VEGF) upregulates BCL-2 and inhibits apoptosis in human and murine mammary adenocarcinoma cells

Abstract

Tumour progression is regulated by the balance of proliferation and apoptosis in the tumour cell population. To date, the role of vascular endothelial growth factor (VEGF) in tumour growth has been attributed to the induction of angiogenesis. VEGF has been shown to be a survival factor for endothelial cells, preventing apoptosis by inducing Bcl-2 expression. In both murine (4T1) and human (MDA-MB-231) metastatic mammary carcinoma cell lines, we found that VEGF upregulated Bcl-2 expression and anti-VEGF antibodies reduced Bcl-2 expression. These alterations in Bcl-2 expression were reflected by the levels of tumour cell apoptosis. VEGF resulted in reduced tumour cell apoptosis, whereas its inhibition with anti-VEGF neutralizing antibodies induced apoptosis directly in tumour cells. Therefore, in addition to its role in angiogenesis and vessel permeability, VEGF acts as a survival factor for tumour cells, inducing Bcl-2 expression and inhibiting tumour cell apoptosis.

References 20

1. 1.
   Identification of a natural soluble neuropilin-1 that binds vascular endothelial growth factor: In vivo expression and antitumor activity · 2000

   Not checked
2. 2.

   Gimbrone M. A., Leapman S. B., Cotran R. S., Folkman J. Tumor dormancy in vivo by prevention of neovascularization. J Exp Med. 1972;136(2):261-276.

   Not in our library10.1084/jem.136.2.261

3. 3.

   Gorski D. H., Beckett M. A., Jaskowiak N. T., Calvin D. P., Mauceri H. J., Salloum R. M., Seetharam S., Koons A., Hari D. M., Kufe D. W. Blockage of the vascular endothelial growth factor stress response increases the antitumor effects of ionizing radiation. Cancer Res. 1999;59(14):3374-3378.

   Not in our library

4. 4.

   Hanahan D., Folkman J. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell. 1996;86(3):353-364.

   Not in our library10.1016/s0092-8674(00)80108-7

5. 5.

   Holmgren L., O'Reilly M. S., Folkman J. Dormancy of micrometastases: balanced proliferation and apoptosis in the presence of angiogenesis suppression. Nat Med. 1995;1(2):149-153.

   Not in our library10.1038/nm0295-149

6. 6.

   Jakeman L. B., Winer J., Bennett G. L., Altar C. A., Ferrara N. Binding sites for vascular endothelial growth factor are localized on endothelial cells in adult rat tissues. J Clin Invest. 1992;89(1):244-253.

   Not in our library10.1172/jci115568

7. 7.

   Katoh O., Takahashi T., Oguri T., Kuramoto K., Mihara K., Kobayashi M., Hirata S., Watanabe H. Vascular endothelial growth factor inhibits apoptotic death in hematopoietic cells after exposure to chemotherapeutic drugs by inducing MCL1 acting as an antiapoptotic factor. Cancer Res. 1998;58(23):5565-5569.

   Not in our library

8. 8.

   Kenyon B. M., Voest E. E., Chen C. C., Flynn E., Folkman J., D'Amato R. J. A model of angiogenesis in the mouse cornea. Invest Ophthalmol Vis Sci. 1996;37(8):1625-1632.

   Not in our library

9. 9.

   Krajewski S., Krajewska M., Turner B. C., Pratt C., Howard B., Zapata J. M., Frenkel V., Robertson S., Ionov Y., Yamamoto H. Prognostic significance of apoptosis regulators in breast cancer. Endocr Relat Cancer. 1999;6(1):29-40.

   Not in our library10.1677/erc.0.0060029

10. 10.

    Li W. W., Grayson G., Folkman J., D'Amore P. A. Sustained-release endotoxin. A model for inducing corneal neovascularization. Invest Ophthalmol Vis Sci. 1991;32(11):2906-2911.

    Not in our library

11. 11.

    Liu R., Page C., Beidler D. R., Wicha M. S., Núez G. Overexpression of Bcl-x(L) promotes chemotherapy resistance of mammary tumors in a syngeneic mouse model. Am J Pathol. 1999;155(6):1861-1867.

    Not in our library10.1016/s0002-9440(10)65505-8

12. 12.

    Matsushita K., Motani R., Sakuta T., Nagaoka S., Matsuyama T., Abeyama K., Maruyama I., Takada H., Torii M. Lipopolysaccharide enhances the production of vascular endothelial growth factor by human pulp cells in culture. Infect Immun. 1999;67(4):1633-1639.

    Not in our library10.1128/iai.67.4.1633-1639.1999

13. 13.

    Mattsby-Baltzer I., Jakobsson A., Sörbo J., Norrby K. Endotoxin is angiogenic. Int J Exp Pathol. 1994;75(3):191-196.

    Not in our library

14. 14.

    Nör J. E., Christensen J., Mooney D. J., Polverini P. J. Vascular endothelial growth factor (VEGF)-mediated angiogenesis is associated with enhanced endothelial cell survival and induction of Bcl-2 expression. Am J Pathol. 1999;154(2):375-384.

    Not in our library10.1016/s0002-9440(10)65284-4

15. 15.

    Oltvai Z. N., Milliman C. L., Korsmeyer S. J. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell. 1993;74(4):609-619.

    Not in our library10.1016/0092-8674(93)90509-o

16. 16.
    The role of endotoxin/lipopolysaccharide in surgically induced tumour growth in a murine model of metastatic disease · 1999

    No notice
17. 17.

    Senger D. R., Galli S. J., Dvorak A. M., Perruzzi C. A., Harvey V. S., Dvorak H. F. Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science. 1983;219(4587):983-985.

    Not in our library10.1126/science.6823562

18. 18.

    Shen B. Q., Lee D. Y., Gerber H. P., Keyt B. A., Ferrara N., Zioncheck T. F. Homologous up-regulation of KDR/Flk-1 receptor expression by vascular endothelial growth factor in vitro. J Biol Chem. 1998;273(45):29979-29985.

    Not in our library10.1074/jbc.273.45.29979

19. 19.

    Soker S., Takashima S., Miao H. Q., Neufeld G., Klagsbrun M. Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor. Cell. 1998;92(6):735-745.

    Not in our library10.1016/s0092-8674(00)81402-6

20. 20.

    Thompson C. B. Apoptosis in the pathogenesis and treatment of disease. Science. 1995;267(5203):1456-1462.

    Not in our library10.1126/science.7878464

Cited by papers we hold 3

• Vascular endothelial growth factor (VEGF) in abdominal fluid in dogs with oncological and non-oncological diseases · 2019
  Not checked
• Implication of Tumor Microenvironment in Chemoresistance: Tumor-Associated Stromal Cells Protect Tumor Cells from Cell Death · 2012
  No notice
• Growth Factor Receptors and Apoptosis Regulators: Signaling Pathways, Prognosis, Chemosensitivity and Treatment Outcomes of Breast Cancer · 2009
  Not checked

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