Biology of Melanoma Metastasis

Abstract

Metastasis is the major cause of death in patients suffering from malignant melanoma, one of the most aggressive types of cancer. Local recurrence is rare in melanoma, but regional and distant metastasis, particularly in the brain, bone, lung and liver, may arise even many years after primary tumor resection, probably due to reactivation of dormant melanoma cells. Dormancy of dispersed melanoma cells is regulated by tumor cell intrinsic as well as extrinsic factors, including angiogenesis, immunosurveillance, and other stroma-dependent processes. Melanoma metastasis correlates with local invasion and the vertical growth phase at the primary site. During this phase, cancer cells invade deep into the dermis and interact with various stromal cells to gain access to blood and lymphatic vessels. Subsequently, melanoma cells migrate along the local lymphatic vasculature, sometimes resulting in locoregional lesions such as in-transit metastases, before reaching the draining lymph node and spreading systemically. Both lymphatic and blood vessels play a critical role in the dispersion of melanomas. Besides providing a simple transport route for cancer cells, endothelial cells are emerging as important and active players in melanoma metastasis. Conditioned by factors derived from the tumor microenvironment, the vasculature undergoes morphological and functional changes, which facilitate the metastatic process in multiple ways. Consequently, therapeutic manipulation of lymphatic and blood vessels may represent a new way to combat melanoma metastasis.