Stromal Cells Present in the Melanoma Niche Affect Tumor Invasiveness and Its Resistance to Therapy

Malignant melanoma is a highly metastatic type of cancer, which arises frequently from transformed pigment cells and melanocytes as a result of long-term UV radiation exposure. In recent years, the incidence of newly diagnosed melanoma patients reached 5% of all cancer cases. Despite the development of novel targeted therapies directed against melanoma-specific markers, patients' response to treatment is often weak or short-term due to a rapid acquisition of drug resistance. Among the factors affecting therapy effectiveness, elements of the tumor microenvironment play a major role. Melanoma niche encompasses adjacent cells, such as keratinocytes, cancer-associated fibroblasts (CAFs), adipocytes, and immune cells, as well as components of the extracellular matrix and tumor-specific physicochemical properties. In this review, we summarize the current knowledge concerning the influence of cancer-associated cells (keratinocytes, CAFs, adipocytes) on the process of melanomagenesis, tumor progression, invasiveness, and the emergence of drug resistance in melanoma. We also address how melanoma can alter the differentiation and activation status of cells present in the tumor microenvironment. Understanding these complex interactions between malignant and cancer-associated cells could improve the development of effective antitumor therapeutic strategies.