The role of angiogenesis in prostate and other urologic cancers: a review

Abstract

Angiogenesis is a process critical to both tumour growth and metastasis. It is a dynamic integrated process involving basement membrane degradation, endothelial cell proliferation and migration, and capillary tubule formation. Under normal circumstances, the microvasculature is maintained in a quiescent state. The acquisition of the angiogenic phenotype depends on the outcome of stimulatory and inhibitory regulation by the tumour and its microenvironment. There are markers of angiogenesis that potentially could provide prognostic information in addition to that gained from conventional clinicopathologic data, and antiangiogenic therapy for urologic cancers has potential advantages over current therapeutic strategies. Promising preclinical studies have led to the initiation of phase I studies of antiangiogenic therapy in combination with chemotherapy, which may lead to novel treatments for urologic malignant tumours and may identify new intermediate markers for the response to therapy.

Fig. 1: Angiogenesis in (A) superficial and (B) muscle-invasive transitional cell carcinoma of the bladder is, in general, illustrative of the process of tumour neovascularization in other cancers. The multiple, sequential and interrelated steps by which angiogenesis is hypothesized to occur involve angiogenic stimuli or lack of endogenous angiogenic inhibitors, or both; the inciting by endothelial cells within venules of local proteolysis to degrade the basement membrane; the protrusion of endothelial cells through the wall of the venule; degradation of the interstitial matrix; continuing movement of endothelial cells toward the angiogenic stimulus; formation by endothelial cells of capillary sprouts that form a lumen; proliferation within sprouts; joining of tips of sprouts; blood flow; and formation of new basement membrane and incorporation of microvascular pericytes. TCC = transitional cell carcinoma, BM = basement membrane.