Profiling Cancer-Associated Fibroblasts in Melanoma

Papaccio, Federica; Kovacs, Daniela; Bellei, Barbara; Caputo, Silvia; Migliano, Emilia; Cota, Carlo; Picardo, Mauro

doi:10.3390/ijms22147255

Cited by 41 publications

(64 citation statements)

References 54 publications

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“…We established two different methods of CAFs acquisition based on commonly utilized systems: using melanoma-conditioned medium [ 36 ] and with melanoma cells present on Transwell inserts [ 37 , 38 ]. Both approaches worked well, leading to fibroblasts’ activation identified by high FAP-α and IL6 levels, which are markers of this type of cells described in the literature [ 34 , 39 , 40 ].…”

Section: Discussionmentioning

confidence: 99%

Melanoma cells with diverse invasive potential differentially induce the activation of normal human fibroblasts

et al. 2022

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Background The tumor microenvironment consists of stromal cells, extracellular matrix, and physicochemical properties (e.g., oxygenation, acidification). An important element of the tumor niche are cancer-associated fibroblasts (CAFs). They may constitute up to 80% of the tumor mass and share some features with myofibroblasts involved in the process of wound healing. CAFs can facilitate cancer progression. However, their interaction with melanoma cells is still poorly understood. Methods We obtained CAFs using conditioned media derived from primary and metastatic melanoma cells, and via co-culture with melanoma cells on Transwell inserts. Using 2D and 3D wound healing assays and Transwell invasion method we evaluated CAFs’ motile activities, while coverslips with FITC-labeled gelatin, gelatin zymography, and fluorescence-based activity assay were employed to determine the proteolytic activity of the examined cells. Western Blotting method was used for the identification of CAFs’ markers as well as estimation of the mediators of MMPs’ (matrix metalloproteinases) expression levels. Lastly, CAFs’ secretome was evaluated with cytokine and angiogenesis proteomic arrays, and lactate chemiluminescence-based assay. Results Acquired FAP-α/IL6-positive CAFs exhibited elevated motility expressed as increased migration and invasion ratio, as well as higher proteolytic activity (area of digestion, MMP2, MMP14). Furthermore, fibroblasts activated by melanoma cells showed upregulation of the MMPs’ expression mediators’ levels (pERK, p-p38, CD44, RUNX), enhanced secretion of lactate, several cytokines (IL8, IL6, CXCL1, CCL2, ICAM1), and proteins related to angiogenesis (GM-CSF, DPPIV, VEGFA, PIGF). Conclusions Observed changes in CAFs’ biology were mainly driven by highly aggressive melanoma cells (A375, WM9, Hs294T) compared to the less aggressive WM1341D cells and could promote melanoma invasion, as well as impact inflammation, angiogenesis, and acidification of the tumor niche. Interestingly, different approaches to CAFs acquisition seem to complement each other showing interactions between studied cells.

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Section: Discussionmentioning

confidence: 99%

Melanoma cells with diverse invasive potential differentially induce the activation of normal human fibroblasts

et al. 2022

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“…Peritumoural fibroblasts can be converted into cancer associated fibroblasts (CAFs), exhibiting analogous properties to myofibroblasts [ 156 ]. During melanoma progression, CAFs may represent an important amount within the tumour cells’ population, displaying variable functions such as immunosuppression, due to TGF-β activity, which include inhibition of migration, maturation, and antigen presentation by DCs, increase in Tregs number, and reduction in the expression of perforin, granzymes, Fas ligand, and IFN-γ in cytotoxic T cells [ 156 ]. Fibroblasts seem to be recruited by tumour cells under β3-adrenergic stimulation by NE [ 151 ].…”

Section: Inflammatory Microenvironment In Malignant Melanomamentioning

confidence: 99%

The Interplay between Tumour Microenvironment Components in Malignant Melanoma

et al. 2022

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Malignant melanoma has shown an increasing incidence during the last two decades, exhibiting a large spectrum of locations and clinicopathological characteristics. Although current histopathological, biochemical, immunohistochemical, and molecular methods provide a deep insight into its biological behaviour and outcome, melanoma is still an unpredictable disease, with poor outcome. This review of the literature is aimed at updating the knowledge regarding melanoma’s clinicopathological and molecular hallmarks, including its heterogeneity and plasticity, involving cancer stem cells population. A special focus is given on the interplay between different cellular components and their secretion products in melanoma, considering its contribution to tumour progression, invasion, metastasis, recurrences, and resistance to classical therapy. Furthermore, the influences of the specific tumour microenvironment or “inflammasome”, its association with adipose tissue products, including the release of “extracellular vesicles”, and distinct microbiota are currently studied, considering their influences on diagnosis and prognosis. An insight into melanoma’s particular features may reveal new molecular pathways which may be exploited in order to develop innovative therapeutic approaches or tailored therapy.

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“…MAFs are a melanoma-derived subtype of cancer-associated fibroblasts (CAFs) [ 1 ]. They are fibroblast-like cells that create a three-dimensional supporting scaffold around melanoma cells [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal-Stromal Cell-like Melanoma-Associated Fibroblasts Increase IL-10 Production by Macrophages in a Cyclooxygenase/Indoleamine 2,3-Dioxygenase-Dependent Manner

Çakır

Hajdara

Széky

et al. 2021

Cancers

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Melanoma-associated fibroblasts (MAFs) are integral parts of melanoma, providing a protective network for melanoma cells. The phenotypical and functional similarities between MAFs and mesenchymal stromal cells (MSCs) prompted us to investigate if, similarly to MSCs, MAFs are capable of modulating macrophage functions. Using immunohistochemistry, we showed that MAFs and macrophages are in intimate contact within the tumor stroma. We then demonstrated that MAFs indeed are potent inducers of IL-10 production in various macrophage types in vitro, and this process is greatly augmented by the presence of treatment-naïve and chemotherapy-treated melanoma cells. MAFs derived from thick melanomas appear to be more immunosuppressive than those cultured from thin melanomas. The IL-10 increasing effect is mediated, at least in part, by cyclooxygenase and indoleamine 2,3-dioxygenase. Our data indicate that MAF-induced IL-10 production in macrophages may contribute to melanoma aggressiveness, and targeting the cyclooxygenase and indoleamine 2,3-dioxygenase pathways may abolish MAF–macrophage interactions.

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Profiling Cancer-Associated Fibroblasts in Melanoma

Cited by 41 publications

References 54 publications

Melanoma cells with diverse invasive potential differentially induce the activation of normal human fibroblasts

Melanoma cells with diverse invasive potential differentially induce the activation of normal human fibroblasts

The Interplay between Tumour Microenvironment Components in Malignant Melanoma

Mesenchymal-Stromal Cell-like Melanoma-Associated Fibroblasts Increase IL-10 Production by Macrophages in a Cyclooxygenase/Indoleamine 2,3-Dioxygenase-Dependent Manner

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