Belviso Immacolata, Pastore Raffaele, Mileo Aldo, Del Genio Emiliano, Boccia Stefania, Palermi Stefano, Sellitto Carmine, Motti Maria Letizia
Department of Psychology and Health Sciences, Telematic University Pegaso, 80143 Naples, Italy.
Department of Medicine and Health Sciences "Vincenzo Tiberio", University of Molise, 86100 Campobasso, Italy.
Int J Mol Sci. 2025 Jun 26;26(13):6132. doi: 10.3390/ijms26136132.
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.
黑色素瘤是最具侵袭性的皮肤癌形式，尽管在过去十年中治疗取得了重大进展，但仍有相当数量的患者最终走向致命结局。黑色素瘤的发生和发展受到黑色素瘤细胞与肿瘤微环境（TME）其他成分之间相互作用的强烈影响。在本综述中，我们重点关注肿瘤微环境中驻留的成纤维细胞与肿瘤细胞之间的相互作用。特别是，我们研究了黑色素瘤细胞诱导驻留成纤维细胞转化为其活性形式（即癌症相关成纤维细胞，CAFs）的分子机制。我们还探讨了CAFs在塑造黑色素瘤微环境（MME）以及构建前转移生态位中的作用，前转移生态位是在远处器官或组织中形成的一种特殊微环境，用于支持转移性黑色素瘤细胞的存活和扩增。最后，我们讨论了旨在破坏CAFs、黑色素瘤细胞和肿瘤微环境其他成分之间相互作用以改善治疗效果的新兴治疗策略。
