Molecular mechanisms of tumor-driven mesenchymal stromal cells differentiation

Mesenchymal stromal cells (MSC) exert either tumor-stimulatory or tumor-inhibitory effect. The alterations in the phenotype of MSC in response to the stimulation by tumor-secreted paracrine factors was analyzed. Melanoma-exposed MSC exhibited the signs of differentiation towards the cells with features of tumor-associated fibroblasts. Paracrine stimulation by glioblastoma secreted factors led to up-regulation of the genes involved in the MSC differentiation. Increased proportion of CD146 (pericytic) and GD2 (neural ganglioside, mesenchymal) positive cells and decreased expression of perivascular marker NG2 in the MSC exposed to tumor-conditioned medium was observed. Melanoma secretome increased MSC migration, glioblastoma secretome compromised angiogenic capacity of MSC in vitro and the protumorigenic effect in vivo. Secreted paracrine factors from melanoma or glioblastoma differently changed molecular traits in MSC, which explains the dual role of MSC in tumor growth.