The role of growth factors, angiogenic enzymes and apoptosis in neovascularization and tumor growth-collected publications.

ABSTRACT

Hemangiomas represent the most frequent tumors of infancy. However, the pathogenesis of these tumors is still largely unknown, and current treatment of juvenile hemangiomas remains unsatisfactory. We have presented a novel animal model for hemangiomas. Induction of hemangioma development was achieved by intraperitoneal (i.p.) infection of 4-day-old rats with the mouse polyoma virus (PyV). This led to the development of multiple hemangiomas, which caused death of the untreated animals within 3 weeks p.i. The hemangiomas had the histological and immunohistochemical features reminiscent of human hemangiomas. Moreover, the angiogenesis inhibitor TNP-470 afforded a protective effect in this model. Tumor growth is determined by the balance between cell proliferation and apoptosis and is modulated by angiogenesis. Angiogenesis is a complex process, involving extensive interplay between cells, extracellular matrix components and soluble factors. Each of these factors represents a possible target for pharmacological intervention to inhibit blood vessel formation and subsequently tumor growth. We have focused on specific inhibitors of the angiogenesis inducers basic fibroblast growth factor and Thymidine Phosphorylase and studied their mechanism of action and anti-angiogenic activity. In addition, we have shown that the apoptosis-inducer cidofovir inhibits PyV-induced hemangioma development in rats and the growth of virus-independent, vascular tumors in mice. So far, cidofovir has only been evaluated clinically for the treatment of human papillomavirus (HPV)-associated tumors. Our findings open new perspectives for the use of cidofovir as an anti-tumor agent in the therapy of hemangiomas and other tumors that are not associated with an oncogenic virus.