Melanoma and the tumor microenvironment.
Melanoma arises through the accrual of mutations in genes critical for proliferation and survival. Although melanoma had been traditionally conceptualized as a cell-autonomous event, increasing evidence supports the notion that these tumors are not isolated entities but rather depend, interact with, and react to the adjacent microenvironment. Melanoma is composed of not only the malignant cells but also the supporting stroma, which includes fibroblasts, endothelial cells, immune cells, soluble molecules, and the extracellular matrix (ECM). Tumor cells actively interact with the microenvironment in a bidirectional manner through molecular signals that modulate the malignant phenotype. This article briefly reviews the molecular basis of melanomagenesis as well as the interplay of melanoma with other cells of the tumor microenvironment and components of the ECM. It also discusses the influence of the microenvironment on therapeutic targeting of melanoma, highlighting recent studies that propose novel strategies to target tumor-microenvironment interactions.
Villanueva
Jessie
J
The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA.
Herlyn
Meenhard
M
D049109:Cell Proliferation; D002470:Cell Survival; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008545:Melanoma / Q000473:pathology* / Q000628:therapy*; D008954:Models, Biological; D008957:Models, Genetic; D009154:Mutation; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic; D010641:Phenotype; D016896:Treatment Outcome
D020782:Matrix Metalloproteinases