Phenotypic and functional similar ities between mesenchymal stem cells and fibroblasts in cancer

The tumor microenvironment (TME) is a major regulator of cancer progression, therapeutic responses, and disease recurrence; it comprises stromal cells, including mesenchymal stem cells (MSCs) and fibroblasts. MSCs and fibroblasts are usually considered separate entities; they share some physical characteristics and functions in cancer. Both cell types actively contribute to tumor progression by modifying the ECM, inducing blood vessel formation, and altering the immune response via various paracrine mechanisms and extracellular vesicles. Recent developments in lineage tracing and single-cell RNA sequencing have highlighted their considerable similarities and functional manifestations, which help explain variability among CAFs. In this paper, we introduce a mechanism and a location matrix to characterize similarities among MSCs, fibroblasts, and CAFs in the tumor microenvironment. Every time there is a change from an MSC-like to a fibroblast-like state, and vice versa, this change is promoted and maintained by pathophysiological (hypoxic), inflammatory, or mechanical stress-induced signals from the tumor microenvironment, thus creating a “stroma that can adapt”. These similarities may influence tumor invasion, metastasis, and resistance to therapy. This narrative review will compile data from the literature concerning the similarities in function, phenotype, and molecular structure between MSCs and fibroblasts in cancer.