**Appendices and nomenclature**

NO nitric oxide

PGE2 prostaglandin


model of Kaposi's sarcoma, Kakhoo et al. reported that MSCs injected intravenously were able to migrate to the tumor and inhibit tumor cell proliferation by inhibiting AKT [32]. On the other hand, they observed in glioma cells that PTEN was upregulated in the presence of HUCBSCs, with the consequent downregulation of AKT [109]. In addition to inhibiting the PI3K/AKT pathway, MSCs can also suppress the WNT/beta-catenin pathway through the induced expression of the pro-apoptotic protein DKK-1 [31, 36, 37]. These recent findings demonstrated that beta-catenin can be negatively regulated in different human carcinoma cell lines (hepatocellular, H7402 and HepG2, breast, MCF-7, hematopoietic, K562 and HL60) by the secretion of DKK-1 by the MSCs. On the other hand, when the activity of DKK-1 was inhibited by the use of anti-DKK-1 neutralizing antibodies or interfering RNA, the inhibitory

Although therapy with MSC in regenerative medicine is considered feasible and safe, the literature reported to date reveals dicrepancies respect to the MSCs impact in the tumor microenvironment. This paradoxical effect could be attributed to the differences in the experimental conditions of isolation and expansion, the source and dose of cells used, the route of administration and its timing, and the host characteristics. This chapter highlights the mechanisms of the effects of tumor support or suppression mediated by the MSCs and analyzes the possible mechanisms involved. MSCs demonstrate a tropism for tumors and once they interact with each other and with cancer cells, they promote tumor growth by: inmunosuppression; promotion of angiogenesis; epithelialmesenchymal transition; inhibition of apoptosis; and promotion of metastasis. In contrast, many studies have reported that MSCs can prevent tumor growth by increasing leukocyte infiltration, inhibiting angiogenesis, suppressing Wnt and AKT signaling. Further investigations are neces-

sary to establish the biosecurity of cell therapy in the presence of precancerous lesions.

effects of MSCs on tumor progression disappeared [31, 36, 37].

74 Stromal Cells - Structure, Function, and Therapeutic Implications

**3. Conclusions**

**Conflict of interest**

Not applicable.

The author discloses no potential conflicts of interest.

**Notes/Thanks/Other declarations**

**Appendices and nomenclature**

NO nitric oxide

PGE2 prostaglandin

