Cancer-Associated Fibroblasts Influence the Biological Properties of Malignant Tumours via Paracrine Secretion and Exosome Production

Abstract

Cancer-associated fibroblasts (CAFs) are an essential component of the tumour microenvironment. They represent a heterogeneous group of cells that are under the control of cancer cells and can reversely influence the cancer cell population. They affect the cancer cell differentiation status, and the migration and formation of metastases. This is achieved through the production of the extracellular matrix and numerous bioactive factors. IL-6 seems to play the central role in the communication of noncancerous and cancer cells in the tumour. This review outlines the role of exosomes in cancer cells and cancer-associated fibroblasts. Available data on the exosomal cargo, which can significantly intensify interactions in the tumour, are summarised. The role of exosomes as mediators of the dialogue between cancer cells and cancer-associated fibroblasts is discussed together with their therapeutic relevance. The functional unity of the paracrine- and exosome-mediated communication of cancer cells with the tumour microenvironment represented by CAFs is worthy of attention.

The Role of IL-6 in Cancer Cell Invasiveness and Metastasis—Overview and Therapeutic Opportunities

“…In in vitro organotypic co-cultures with human fibroblasts and a human skin carcinogenesis model (HaCaT-ras A-5RT1 cell line), IL-6 was found to activate fibroblasts and encourage progression to the tumour-associated fibroblast phenotype, activating expression of metalloproteinase-2, thus promoting the invasive capabilities [ 158 ]. In addition to paracrine signalling, exosomes produced by melanoma cells stimulated the production of IL-6 by CAFs, which improved in vitro migration of melanoma cells from the heterogeneous spheroids containing melanoma cells and CAFs in 3D collagen gels [ 159 , 160 ].…”

Autoimmunity, cancer and COVID-19 abnormally activate wound healing pathways: critical role of inflammation

“…CAFs may arise from normal resident tissue fibroblasts (recruited and activated by malignant cells), similarly to myofibroblasts arising from normal dermal fibroblasts in a wound. However, CAFs can also be derived from a wider panel of potential precursors such as mesenchymal stem cells, adipocytes, stellate cells, circulating fibrocytes, pericytes, mesothelial cells and epithelial and endothelial cells following exposure to potent pro-inflammatory factors (Liu et al 2019), including but not limited to IL-1β, TGF-β and platelet-derived growth factor (PDGF) (Vokurka et al 2022).…”

“…SMA (Fig. 3) and fibroblast activation protein alpha (FAP) seem to be widely accepted and stable markers of CAFs, separating CAFs from the larger pool of fibroblasts present in the body (Nurmik et al 2020;Vokurka et al 2022).…”

Expression of Selected miRNAs in Normal and Cancer-Associated Fibroblasts and in BxPc3 and MIA PaCa-2 Cell Lines of Pancreatic Ductal Adenocarcinoma

“…The structural roles of CAFs include the production and simultaneous remodelling of the extracellular matrix [ 2 , 3 ]. Concerning the proportion of distinct cell types present in PDAC tumors, CAFs represent an outstandingly abundant cell type.…”

“…Regarding their origin, CAFs can arise from local fibroblasts. However, their origin in mesenchymal stem cells, pericytes, or stellate cells under the control of cancer cells has also been observed [ 3 ].…”