Onkológia 4/2013

Multipotent cell-mediated drug resistance

Solid tumors can be considered as „an indepedent tisssue of the body“ being composed from malignant cells and non-malignant compartment. The latter usually comprehensively designated as tumor microenvironment is composed from tumor vasculature, endothelial cells, cells of the immune system, stromal cells and tumor associated fibroblasts, which can differentiate from multipotent mesenchymal stromal cells (MSC). These two components together dictate the tumor biology and responses to the cytotoxic treatment. Tumor microenvironment regulates drug sensitivity by production of secreted factors in response to drug exposure which can cause increased invasiveness and migration in line with decreased apoptosis and drug sensitivity in cancer cells. Recently, the experiments elucidating a role of MSC in the tumor biology demonstrated the capability of these cells to affect multiple hallmarks of cancer such as angiogenesis, metastasis, apoptosis, pro-survival and evasion of the immune system. MSC as one of the component in the tumor stroma and precursors of tumor-associated fibroblasts were also shown to increase the chemoresistance. Moreover, experimental data indicated that the effect is mediated by the soluble factors secreted from circulating MSC upon drug exposure and results in systemic chemotherapy resistance. MSC are very important regulators of tumor growth and therefore their impact on tumor treatment should be further elucidated in detail in order to find measures how to prevent treatment failure in clinical situation.

Keywords: human mesenchymal cells, multipotent cells, stromal cells, tumor microenvironment, chemoresistance.