Profiling Cancer-Associated Fibroblasts in Melanoma

• Published in: International journal of molecular sciences 2021-07, Vol.22 (14), p.7255
• Main Authors: Papaccio, Federica, Kovacs, Daniela, Bellei, Barbara, Caputo, Silvia, Migliano, Emilia, Cota, Carlo, Picardo, Mauro
• Format: Article
• Language: English
• Subjects: Angiogenesis; Biomarkers, Tumor - genetics; CAF; Cancer therapies; Cancer-Associated Fibroblasts - metabolism; Cell adhesion & migration; Cell culture; Cell Line, Tumor; Cell Movement - genetics; Cell Proliferation - genetics; Chemokines; Chemotherapy; Coculture Techniques; Complex systems; Crosstalk; Cytokines; Cytokines - genetics; Cytotoxicity; Drug resistance; Extracellular matrix; Extracellular Matrix - genetics; Fibroblasts; Gene expression; Gene Expression Profiling - methods; Gene Expression Regulation, Neoplastic - genetics; Growth factors; Humans; Inflammation; Inflammation - genetics; Inflammatory response; Kinases; Ligands; Medical prognosis; Melanoma; Melanoma - genetics; Melanoma, Cutaneous Malignant; Metastases; Metastasis; Motility; Phenotypes; Proteins; Skin cancer; Skin Neoplasms - genetics; Solid tumors; stroma; Stromal cells; Stromal Cells - metabolism; Systems analysis; Tumor microenvironment; Tumor necrosis factor-TNF; Tumors
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22147255

Solid tumors are complex systems characterized by dynamic interactions between neoplastic cells, non-tumoral cells, and extracellular components. Among all the stromal cells that populate tumor microenvironment, fibroblasts are the most abundant elements and are critically involved in disease progression. Cancer-associated fibroblasts (CAFs) have pleiotropic functions in tumor growth and extracellular matrix remodeling implicated in local invasion and distant metastasis. CAFs additionally participate in the inflammatory response of the tumor site by releasing a variety of chemokines and cytokines. It is becoming clear that understanding the dynamic, mutual melanoma-fibroblast relationship would enable treatment options to be amplified. To better characterize melanoma-associated fibroblasts, here we analyzed low-passage primary CAFs derived from advanced-stage primary skin melanomas, focusing on the immuno-phenotype. Furthermore, we assessed the expression of several CAF markers and the production of growth factors. To deepen the study of CAF-melanoma cell crosstalk, we employed CAF-derived supernatants and trans-well co-culture systems to evaluate the influences of CAFs on (i) the motogenic ability of melanoma cells, (ii) the chemotherapy-induced cytotoxicity, and (iii) the release of mediators active in modulating tumor growth and spread.