Characterization of tumor-derived mesenchymal stem cells potentially differentiating into cancer-associated fibroblasts in lung cancer

Abstract Purpose The goal of this study was to understand if mesenchymal stem cells isolated from lung tumor tissue (T-MSCs) may differentiate into cancer associated fibroblasts (CAFs), that promote neoplastic progression, angiogenesis and metastasis in the epithelial solid tumors, mimicking the tumor microenvironmental influence. Methods MSCs were been obtained from healthy (Control, C-MSCs) and tumor (T-MSCs) tissue of one patient who underwent a lobectomy for a lung adenocarcinoma pT1bN0. Isolated cells were characterized for the presence of molecular markers (identified by routine diagnostic characterization in differentiated tumoral cells), stemness properties, and CAF-related markers expression. Subsequently, cells were co-cultured with a lung adenocarcinoma cell line (A549 cells) to evaluate the effects on proliferation, oncogene expression and IL6 secretion. Results C- and T-MSCs did not present EGFR mutations unlike tumor tissue and showed a stem-like immunophenotype, characterized by the ability to differentiate towards osteo-, chondro- and adipogenic lineages. The expression of markers referred to CAFs (α-SMA, HI-1α, MMP11, VEGF, CXCL12, TGF-β1, TGF-βRII, IL6, TNFα) was significantly higher in T-MSCs than in C-MSCs. The co-cultures with A549 cells led to the over-expression of selected oncogenes and to the increase of IL6 secretion in T-MSCs but not in C-MSCs. Conclusions MSCs isolated from tumor tissue displayed distinct properties compared to MSCs isolated from healthy tissue, suggesting T-MSCs differentiation towards a CAF-related phenotype under the influence of the tumoral microenvironment.