Angiogenesis, lymphangiogenesis, and melanoma metastasis.

The induction of angiogenesis is a critical point in the development of most human tumors - including melanomas. Some of the earliest studies in the field of tumor angiogenesis showed that transplantation of human melanoma fragments into the hamster cheek pouch stimulated blood vessel growth. Since then, numerous studies have demonstrated that human melanomas also induce angiogenesis. The prognostic importance of the degree of melanoma vascularization, however, has remained controversial. Elevated expression of several angiogenic factors, including vascular endothelial growth factor, basic fibroblast growth factor, and interleukin-8, has been detected in primary cutaneous melanomas, and the importance of these mediators in promoting melanoma angiogenesis and metastasis has been confirmed in tumor xenotransplant models. Based upon these findings, several clinical trials of angiogenesis inhibitors have been initiated in human melanoma patients and are currently underway. Recent experimental evidence indicates that tumor-associated lymphangiogenesis also plays an important role in mediating tumor spread to regional lymph nodes. These observations have important implications for prognosis and treatment of human melanomas.