The initiation and progression of various types of tumors, such as lung neoplasms, are driven by a population of cells with stem cell properties and their microenvironment. Bone marrow mesenchymal stem cells (BM-MSCs) in long-term in vitro culture may exhibit spontaneous changes in stem cell biological properties, including malignant transformations; however, the molecular mechanisms of this have not been fully elucidated. In the present study, a BM-MSC and lung cancer A549 cell co-culture system was utilized to investigate how the tumor microenvironment may spontaneously change the proliferation, migration and differentiation of BM-MSCs. It was demonstrated that the lung cancer A549 microenvironment is able to induce changes in the cell morphology, proliferation, karyotype, cytoskeleton and migration ability of BM-MSCs in vitro. Compared with the control group BM-MSCs, the expression of Ras, phosphorylated-extracellular regulated protein kinases, nuclear factor-κB, P62 and B-cell lymphoma 2 (Bcl-2) proteins in groups of co-cultured BM-MSCs increased significantly (P<0.05) and the expression of P53, Bcl-2 associated X protein and caspase-3 protein decreased significantly (P<0.05). The mechanisms responsible for the changes observed in BM-MSCs may be related to abnormal expression of related genes in the ERK signaling pathway.
Keywords: bone marrow mesenchymal stem cells; co-culture; lung cancer A549; migration; proliferation.