Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 22, Issue 10, Pages -Publisher
MDPI
DOI: 10.3390/ijms22105283
Keywords
melanoma; tumor microenvironment; fibroblasts; melanoma-associated fibroblasts
Funding
- Italian Ministry of Education, Universities and Research [PRIN-20177TTP3S]
- Regione Campania SATIN grant
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Cutaneous melanoma tissue is a network of cancer cells and tumor microenvironment characterized by high structural and cellular plasticity. The interactions between TME components and cancer cells lead to dramatic alterations in ECM remodelling, stromal cell phenotypes, and therapeutic responses. Melanoma-associated fibroblasts (MAFs) and normal fibroblasts within TME play crucial roles in influencing melanoma growth and outcomes through their cellular interactions and secretory profiles.
Cutaneous melanoma (CM) tissue represents a network constituted by cancer cells and tumor microenvironment (TME). A key feature of CM is the high structural and cellular plasticity of TME, allowing its evolution with disease and adaptation to cancer cell and environmental alterations. In particular, during melanoma development and progression each component of TME by interacting with each other and with cancer cells is subjected to dramatic structural and cellular modifications. These alterations affect extracellular matrix (ECM) remodelling, phenotypic profile of stromal cells, cancer growth and therapeutic response. The stromal fibroblast populations of the TME include normal fibroblasts and melanoma-associated fibroblasts (MAFs) that are highly abundant and flexible cell types interacting with melanoma and stromal cells and differently influencing CM outcomes. The shift from the normal microenvironment to TME and from normal fibroblasts to MAFs deeply sustains CM growth. Hence, in this article we review the features of the normal microenvironment and TME and describe the phenotypic plasticity of normal dermal fibroblasts and MAFs, highlighting their roles in normal skin homeostasis and TME regulation. Moreover, we discuss the influence of MAFs and their secretory profiles on TME remodelling, melanoma progression, targeted therapy resistance and immunosurveillance, highlighting the cellular interactions, the signalling pathways and molecules involved in these processes.
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