Bidirectional and opposite effects of naïve mesenchymal stem cells on tumor growth and progression

Cancer has long been considered as a heterogeneous population of uncontrolled proliferation of
different transformed cell types. The recent findings concerning tumorigeneses have highlighted
the fact that tumors can progress through tight relationships among tumor cells, cellular, and
non-cellular components which are present within tumor tissues. In recent years, studies have
shown that mesenchymal stem cells (MSCs) are essential components of non-tumor cells within
the tumor tissues that can strongly affect tumor development. Several forms of MSCs have been
identified within tumor stroma. Naïve (innate) mesenchymal stem cells (N-MSCs) derived from
different sources are mostly recruited into the tumor stroma. N-MSCs exert dual and divergent
effects on tumor growth through different conditions and factors such as toll-like receptor
priming (TLR-priming), which is the primary underlying causes of opposite effects. Moreover,
MSCs also have the contrary effects by various molecular mechanisms relying on direct cell-
to-cell connections and indirect communications through the autocrine, paracrine routes, and
tumor microenvironment (TME).
Overall, cell-based therapies will hold great promise to provide novel anticancer treatments.
However, the application of intact MSCs in cancer treatment can theoretically cause adverse
clinical outcomes. It is essential that to extensively analysis the effective factors and conditions
in which underlying mechanisms are adopted by MSCs when encounter with cancer.
The aim is to review the cellular and molecular mechanisms underlying the dual effects of
MSCs followed by the importance of polarization of MSCs through priming of TLRs.