Targeting vasculature in urologic tumors: Mechanistic and therapeutic significance

Division of Urology and Department of Molecular Biochemistry, and Markey Cancer Center, University of Kentucky College of Medicine, Lexington, Kentucky, USA.
Journal of Cellular Biochemistry (Impact Factor: 3.26). 02/2008; 103(3):691-708. DOI: 10.1002/jcb.21442
Source: PubMed


Recent advances toward understanding the molecular mechanisms regulating cancer initiation and progression provide new insights into the therapeutic value of targeting tumor vascularity by interfering with angiogenic signaling pathways. The functional contribution of key angiogenic factors toward increased vascularity characterizing metastatic tumors and their therapeutic exploitation is considered in three major urologic malignancies, renal, bladder, and prostate cancer. With the realization that the success of the therapeutic efficacy of the various anti-angiogenic approaches for the treatment of urologic tumors has yet to be proven clinically, the challenge remains to select critical angiogenesis pathways that can be targeted for an individual tumor. Here we discuss the major mechanisms that support formation of vasculature in renal, bladder, and prostate tumors and the current results of targeting of specific molecules/regulators for therapeutic intervention against metastastic disease.

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Available from: Shinichi Sakamoto, Oct 10, 2015
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    • "The leading front of migrating cells is driven by enhanced proliferation of ECs. This is then followed by re-organization of ECs to form tubules with a central lumen, together with the recruitment of periendothelial cells (pericytes) and vascular smooth muscle cells for new capillary stabilization (37). The RhoA/ROCK pathway plays a role in each of these key steps (Fig. 2). "
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    • "This is followed by migration of endothelial cells and chemoattraction [12]. This leading front of migrating cells is driven by enhanced proliferation of endothelial cells, followed by formation of capillary tubes via organization of the endothelial cells, and a recruitment of pericytes and vascular smooth muscle cells for capillary stabilization [25]. "
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    • "Thus, MKP5 induction and VEGF suppression by calcitriol could further contribute to its anti-angiogenic effects through p38 inactivation. MMPs promote angiogenesis by mediating the degradation of the basement membrane of the vascular epithelium and the extracellular matrix, thereby creating a passageway in these barriers for the formation of new capillaries (Sakamoto et al. 2008). "
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