Cancer-associated-fibroblasts and tumour cells: a diabolic liaison driving cancer progression

Abstract

Several recent papers have now provided compelling experimental evidence that the progression of tumours towards a malignant phenotype does not depend exclusively on the cell-autonomous properties of cancer cells themselves but is also deeply influenced by tumour stroma reactivity, thereby undergoing a strict environmental control. Tumour microenvironmental elements include structural components such as the extracellular matrix or hypoxia as well as stromal cells, either resident cells or recruited from circulating precursors, as macrophages and other inflammatory cells, endothelial cells and cancer-associated fibroblasts (CAFs). All these elements synergistically play a specific role in cancer progression. This review summarizes our current knowledge on the role of CAFs in tumour progression, with a particular focus on the biunivocal interplay between CAFs and cancer cells leading to the activation of the epithelial-mesenchymal transition programme and the achievement of stem cell traits, as well as to the metabolic reprogramming of both stromal and cancer cells. Recent advances on the role of CAFs in the preparation of metastatic niche, as well as the controversial origin of CAFs, are discussed in light of the new emerging therapeutic implications of targeting CAFs.

3-Dimensional Patient-Derived Lung Cancer Assays Reveal Resistance to Standards-of-Care Promoted by Stromal Cells but Sensitivity to Histone Deacetylase Inhibitors

“…Patientderived CAFs when screened in 3D coculture broadly increase proliferation of standard cell lines, and we and others also observed a similar trend with bone marrow-derived MSCs, which are one of the putative origins of cancer-associated stem cells (41). CAFs have been implicated in growth promotion, EMT, metastasis, and drug resistance, not least in the era of TKIs (32,42) and thus their incorporation into the assay seems the first logical step in constructing multicell type ex vivo assays.…”

Mesenchymal stem cells in tumor development

“…They have been associated with poor patient prognosis 169,170 and are implicated in serving a multitude of pro-malignant activities, including, for example, the ability to enhance angiogenesis and to foster ECM remodeling (reviewed in ref. 171). The notion that MSCs generate CAF populations is highly interesting and holds the potential of shedding much needed light on the origin(s) of CAFs and on the fate of MSCs once recruited into the tumor microenvironment.…”

The next step: mechanisms driving adrenocortical carcinoma metastasis

“…As they contain proteins, lipids, DNA, mRNA and miRNAs, they have been suggested to play a pivotal role in exchanging information between cells, in particular between tumor cells and their microenvironment. Indeed, the tumor cells 'educate' the surrounding stromal cells in the microenvironment (fibroblasts, endothelial cells, preadipocytes) to modify their functions and metabolism in order to support tumor progression (Cirri & Chiarugi 2012, Chiarugi & Cirri 2016. On the other hand, the surrounding stroma responds and interacts with the tumor cells exchanging pivotal factors through these exosomal cargoes.…”