Although mesenchymal stem cells (MSCs) are considered to be the cells of origin for most
sarcomas, the role of MSCs as a source of
tumor stroma is not fully understood in this
tumor type. The current study investigated whether MSCs affect the
tumor growth and metastatic ability in rat
osteosarcoma model. Results from subcutaneous co-implantation of rat
osteosarcoma COS1NR cells, established in our laboratory, with rat MSCs isolated from femur bone marrow showed that the incidence of
tumor formation and
tumor growth rate was higher until 5 weeks compared to COS1NR cell inoculation alone. However, no difference was observed in
tumor growth afterwards and in the number of metastatic nodules at 9 weeks (0.75 vs. 1.2). Intravenous MSC injection at weeks 3 and 5 after subcutaneous inoculation of COS1NR cells significantly increased the number of lung nodules in the group with MSC injection compared to the group without MSC injection (17.33 vs. 2.0), while no difference was observed in subcutaneous
tumor growth between those groups. Pathway analysis from gene expression profile identified that genes involved in focal adhesion,
cytokine-
cytokine receptor and
extracellular matrix-receptor pathways such as CAMs (ICAM and VCAM)-
integrins were highly expressed in MSCs, possibly participating in the
tumor progression of
osteosarcoma. These results suggest that MSCs could provide a source of microenvironments for
osteosarcoma cells, and might enhance the ability of settlement and colonization which lead to early onset of growth and
metastasis, possibly through their activated pathways interaction.