The Role of Fibroblasts in Melanoma Development: From Tumor Microenvironment Remodeling to Pre-Metastatic Niche Formation.

Melanoma is the most aggressive form of skin cancer, and despite significant therapeutic advances over the past decade, a substantial number of patients still progress to a fatal outcome. The initiation and progression of melanoma are strongly influenced by interactions between melanoma cells and other components of the tumor microenvironment (TME). In this review, we focus on the interplay between fibroblasts resident in the tumor microenvironment and tumor cells. In particular, we examine the molecular mechanisms through which melanoma cells induce the transformation of resident fibroblasts into their active form, known as cancer-associated fibroblasts (CAFs). We also explore the role of CAFs in shaping the melanoma microenvironment (MME) and in organizing the pre-metastatic niche, a specialized microenvironment that forms in distant organs or tissues to support the survival and expansion of metastatic melanoma cells. Finally, we discuss emerging therapeutic strategies aimed at disrupting the interactions between CAFs, melanoma cells, and other components of the tumor microenvironment to improve treatment outcomes.