Influence of the microenvironment on melanoma cell fate determination and phenotype.

Tumor cells communicate bidirectionally with the surrounding microenvironment, sending and receiving topographical and molecular cues that direct diverse cellular phenomena, including differentiation, growth, and invasion. The microenvironment has long been acknowledged as a facilitator of melanoma progression, and recent studies have illuminated tumor-associated factors, including hypoxia and the extracellular matrix, as important mediators of melanocyte transformation and transdifferentiation. Although these findings portray the microenvironment as a perilous obstacle to the successful treatment of advanced melanomas, it is important to note that certain molecular milieus may be capitalized on as potential treatment modalities. Indeed, our group and others have elucidated the unique ability of embryonic microenvironments to normalize aggressive melanoma cells toward a more benign melanocytic phenotype. The microenvironment therefore presents a novel target for the treatment and ultimately the prevention of melanoma progression and metastasis.