Influence of Tumor Microenvironment and Fibroblast Population Plasticity on Melanoma Growth, Therapy Resistance and Immunoescape

被引:40
|
作者
Romano, Veronica [1 ]
Belviso, Immacolata [1 ]
Venuta, Alessandro [1 ]
Ruocco, Maria Rosaria [2 ]
Masone, Stefania [3 ]
Aliotta, Federica [2 ]
Fiume, Giuseppe [4 ]
Montagnani, Stefania [1 ]
Avagliano, Angelica [1 ,5 ]
Arcucci, Alessandro [1 ]
机构
[1] Univ Napoli Federico II, Dept Publ Hlth, I-80131 Naples, Italy
[2] Univ Naples Federico II, Dept Mol Med & Med Biotechnol, I-80131 Naples, Italy
[3] Univ Naples Federico II, Dept Clin Med & Surg, I-80131 Naples, Italy
[4] Magna Graecia Univ Catanzaro, Dept Expt & Clin Med, I-88100 Catanzaro, Italy
[5] Univ Napoli Federico II, Dept Struct Engn & Architecture, I-80125 Naples, Italy
关键词
melanoma; tumor microenvironment; fibroblasts; melanoma-associated fibroblasts; CANCER-ASSOCIATED FIBROBLASTS; EPITHELIAL-MESENCHYMAL TRANSITION; T-CELL RESPONSES; DERMAL FIBROBLASTS; STROMAL FIBROBLASTS; ACTIVATION PROTEIN; MALIGNANT-MELANOMA; DOWN-REGULATION; IN-VITRO; MATRIX METALLOPROTEINASE-2;
D O I
10.3390/ijms22105283
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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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页数:24
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