This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Langley, R. R. Articles by Fidler, I. J. Search for Related Content PubMed PubMed Citation Articles by Langley, R. R. Articles by Fidler, I. J.

Activation of the Platelet-Derived Growth Factor-Receptor Enhances Survival of Murine Bone Endothelial Cells¹

Department of Cancer Biology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas

The activation of the microvascular endothelial cell platelet-derived growth factor (PDGF) receptor (PDGF-R) by PDGF has been implicated in neoplastic angiogenesis. Here, we established cultures of murine bone microvascular endothelial cells and examined their response to stimulation with PDGF BB ligand and to blockade of PDGF-R signaling with the tyrosine kinase inhibitor STI571 (Gleevec). The addition of STI571 to cultures of bone endothelial cells blocked PDGF BB-induced phosphorylation in a dose-dependent manner and completely abrogated the activation of downstream targets Akt and ERK1/2. Coadministration of STI571 and Taxol also induced the activation of procaspase-3 and significant apoptosis. These data suggest that phosphorylation of PDGF-R stimulates survival pathways in bone endothelial cells and that by selectively inhibiting PDGF-R signaling with STI571, the cells are rendered sensitive to Taxol treatment. The therapeutic combination of STI571 and Taxol may be a powerful tool for targeting tumor-associated endothelial cells in the skeletal compartment.

This article has been cited by other articles:

				K. J Woad, A. J Hammond, M. Hunter, G. E Mann, M. G Hunter, and R. S Robinson FGF2 is crucial for the development of bovine luteal endothelial networks in vitro Reproduction, September 1, 2009; 138(3): 581 - 588. [Abstract] [Full Text] [PDF]

				V. Ramachandran, T. Arumugam, H. Wang, and C. D. Logsdon Anterior Gradient 2 Is Expressed and Secreted during the Development of Pancreatic Cancer and Promotes Cancer Cell Survival Cancer Res., October 1, 2008; 68(19): 7811 - 7818. [Abstract] [Full Text] [PDF]

				C. J. Logothetis, N. M. Navone, and S.-H. Lin Understanding the Biology of Bone Metastases: Key to the Effective Treatment of Prostate Cancer Clin. Cancer Res., March 15, 2008; 14(6): 1599 - 1602. [Abstract] [Full Text] [PDF]

				W. Wu, M. S. O'Reilly, R. R. Langley, R. Z. Tsan, C. H. Baker, N. Bekele, X. M. Tang, A. Onn, I. J. Fidler, and R. S. Herbst Expression of epidermal growth factor (EGF)/transforming growth factor-{alpha} by human lung cancer cells determines their response to EGF receptor tyrosine kinase inhibition in the lungs of mice Mol. Cancer Ther., October 1, 2007; 6(10): 2652 - 2663. [Abstract] [Full Text] [PDF]

				R. R. Langley and I. J. Fidler Tumor Cell-Organ Microenvironment Interactions in the Pathogenesis of Cancer Metastasis Endocr. Rev., May 1, 2007; 28(3): 297 - 321. [Abstract] [Full Text] [PDF]

				S.-J. Kim, H. Uehara, S. Yazici, J. E. Busby, T. Nakamura, J. He, M. Maya, C. Logothetis, P. Mathew, X. Wang, et al. Targeting platelet-derived growth factor receptor on endothelial cells of multidrug-resistant prostate cancer. J Natl Cancer Inst, June 7, 2006; 98(11): 783 - 793. [Abstract] [Full Text] [PDF]

				A. Lee, J. Frischer, A. Serur, J. Huang, J.-O Bae, Z. N. Kornfield, L. Eljuga, C. J. Shawber, N. Feirt, M. Mansukhani, et al. Inhibition of cyclooxygenase-2 disrupts tumor vascular mural cell recruitment and survival signaling. Cancer Res., April 15, 2006; 66(8): 4378 - 4384. [Abstract] [Full Text] [PDF]

				D. Faraone, M. S. Aguzzi, G. Ragone, K. Russo, M. C. Capogrossi, and A. Facchiano Heterodimerization of FGF-receptor 1 and PDGF-receptor-{alpha}: a novel mechanism underlying the inhibitory effect of PDGF-BB on FGF-2 in human cells Blood, March 1, 2006; 107(5): 1896 - 1902. [Abstract] [Full Text] [PDF]

				T. Zhang, H.-C. Sun, Y. Xu, K.-Z. Zhang, L. Wang, L.-X. Qin, W.-Z. Wu, Y.-K. Liu, S.-L. Ye, and Z.-Y. Tang Overexpression of Platelet-Derived Growth Factor Receptor {alpha} in Endothelial Cells of Hepatocellular Carcinoma Associated with High Metastatic Potential Clin. Cancer Res., December 15, 2005; 11(24): 8557 - 8563. [Abstract] [Full Text] [PDF]

				K. Yokoi, T. Sasaki, C. D. Bucana, D. Fan, C. H. Baker, Y. Kitadai, T. Kuwai, J. L. Abbruzzese, and I. J. Fidler Simultaneous Inhibition of EGFR, VEGFR, and Platelet-Derived Growth Factor Receptor Signaling Combined with Gemcitabine Produces Therapy of Human Pancreatic Carcinoma and Prolongs Survival in an Orthotopic Nude Mouse Model Cancer Res., November 15, 2005; 65(22): 10371 - 10380. [Abstract] [Full Text] [PDF]

				C. V. Ustach and H.-R. C. Kim Platelet-Derived Growth Factor D Is Activated by Urokinase Plasminogen Activator in Prostate Carcinoma Cells Mol. Cell. Biol., July 15, 2005; 25(14): 6279 - 6288. [Abstract] [Full Text] [PDF]

				S.-J. Kim, H. Uehara, S. Yazici, J. He, R. R. Langley, P. Mathew, D. Fan, and I. J. Fidler Modulation of Bone Microenvironment with Zoledronate Enhances the Therapeutic Effects of STI571 and Paclitaxel against Experimental Bone Metastasis of Human Prostate Cancer Cancer Res., May 1, 2005; 65(9): 3707 - 3715. [Abstract] [Full Text] [PDF]

				K. Yokoi, P. H. Thaker, S. Yazici, R. R. Rebhun, D.-H. Nam, J. He, S.-J. Kim, J. L. Abbruzzese, S. R. Hamilton, and I. J. Fidler Dual Inhibition of Epidermal Growth Factor Receptor and Vascular Endothelial Growth Factor Receptor Phosphorylation by AEE788 Reduces Growth and Metastasis of Human Colon Carcinoma in an Orthotopic Nude Mouse Model Cancer Res., May 1, 2005; 65(9): 3716 - 3725. [Abstract] [Full Text] [PDF]

				M. von Mehren Targeted Therapy With Imatinib: Hits and Misses? J. Clin. Oncol., January 1, 2005; 23(1): 8 - 10. [Full Text] [PDF]