| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Molecular Biology, Pathobiology, and Genetics |
1 Angiogenesis Research Laboratory, Department of Restorative Sciences, University of Michigan School of Dentistry; 2 Departments of Dermatology and 3 Pathology, University of Michigan School of Medicine; 4 Department of Biomedical Engineering, University of Michigan College of Engineering; 5 Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan; 6 Department of Restorative Sciences, Tokyo Medical and Dental University, Tokyo, Japan; 7 Departments of Pathology, Medicine, and Radiation and Cellular Oncology, University of Chicago School of Medicine, Chicago, Illinois; and 8 Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia
Requests for reprints: Jacques E. Nör, Angiogenesis Research Laboratory, University of Michigan School of Dentistry, Room 2309, 1011 North University, Ann Arbor, MI 48109-1078. Phone: 734-936-9300; Fax: 734-936-1597; E-mail: jenor{at}umich.edu.
The current understanding of the interaction between the endothelium and cancer cells is fundamentally based on the concept that endothelial cells are responsive to differentiation and survival signals originating from the tumor cells. Whereas the effect of tumor cell–secreted factors on angiogenesis is well established, little is known about the effect of factors secreted by endothelial cells on tumor cell gene expression and tumor progression. Here, we show that bcl-2 gene expression is significantly higher in the tumor-associated endothelial cells of patients with head and neck squamous cell carcinomas (HNSCC) as compared with endothelial cells from the normal oral mucosa. Bcl-2 induces vascular endothelial growth factor (VEGF) expression in neovascular endothelial cells through a signal transducer and activator of transcription 3 (STAT3)–mediated pathway. Endothelial cell–derived VEGF signals through VEGFR1 and induces expression of Bcl-2 and the proangiogenic chemokines CXCL1 and CXCL8 in HNSCC cells. Notably, inhibition of Bcl-2 expression in neovascular endothelial cells with RNA interference down-regulates expression of Bcl-2, CXCL8, and CXCL1 in HNSCC cells, and is sufficient to inhibit growth and decrease the microvessel density of xenografted HNSCC in immunodeficient mice. Together, these results show that Bcl-2 is the orchestrator of a cross-talk between neovascular endothelial cells and tumor cells, which has a direct effect on tumor growth. This work identifies a new function for Bcl-2 in cancer biology that is beyond its classic role in cell survival. [Cancer Res 2007;67(20):9685–93]
This article has been cited by other articles:
![]() |
M. C. BOSCO, S. DELFINO, F. FERLITO, M. PUPPO, A. GREGORIO, C. GAMBINI, M. GATTORNO, A. MARTINI, and L. VARESIO The Hypoxic Synovial Environment Regulates Expression of Vascular Endothelial Growth Factor and Osteopontin in Juvenile Idiopathic Arthritis J Rheumatol, June 1, 2009; 36(6): 1318 - 1329. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. Ashimori, B. D. Zeitlin, Z. Zhang, K. Warner, I. M. Turkienicz, A. C. Spalding, T. N. Teknos, S. Wang, and J. E. Nor TW-37, a small-molecule inhibitor of Bcl-2, mediates S-phase cell cycle arrest and suppresses head and neck tumor angiogenesis Mol. Cancer Ther., April 1, 2009; 8(4): 893 - 903. [Abstract] [Full Text] [PDF] |
||||
![]() |
Z. Wang, A. S. Azmi, A. Ahmad, S. Banerjee, S. Wang, F. H. Sarkar, and R. M. Mohammad TW-37, a Small-Molecule Inhibitor of Bcl-2, Inhibits Cell Growth and Induces Apoptosis in Pancreatic Cancer: Involvement of Notch-1 Signaling Pathway Cancer Res., April 1, 2009; 69(7): 2757 - 2765. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Miyazawa, Z. Dong, Z. Zhang, K.G. Neiva, M.M. Cordeiro, D.T. Oliveira, and J.E. Nor Effect of PTK/ZK on the Angiogenic Switch in Head and Neck Tumors Journal of Dental Research, December 1, 2008; 87(12): 1166 - 1171. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. L. Nachman and S. Rafii Platelets, Petechiae, and Preservation of the Vascular Wall N. Engl. J. Med., September 18, 2008; 359(12): 1261 - 1270. [Full Text] [PDF] |
||||
![]() |
B. D. Zeitlin, I. J. Zeitlin, and J. E. Nor Expanding Circle of Inhibition: Small-Molecule Inhibitors of Bcl-2 as Anticancer Cell and Antiangiogenic Agents J. Clin. Oncol., September 1, 2008; 26(25): 4180 - 4188. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Kaneko, T. Okiji, R. Kaneko, J.E. Nor, and H. Suda Antigen-presenting Cells in Human Radicular Granulomas Journal of Dental Research, June 1, 2008; 87(6): 553 - 557. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |