title: Mesenchymal stem cells promote tumor engraftment and metastatic colonization             in rat osteosarcoma model.
abstract: 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.
authors.affiliation: Department of Orthopedic Surgery, Nara Medical University, 840                     Shijo-cho, Kashihara, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Tsukamoto
authors.forename: Kanya
authors.initials: K
authors.lastname: Honoki
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Fujii
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Tohma
authors.forename: Akira
authors.initials: A
authors.lastname: Kido
authors.forename: Toshio
authors.initials: T
authors.lastname: Mori
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Tsujiuchi
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Tanaka
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement / Q000502:physiology; D020869:Gene Expression Profiling; D008175:Lung Neoplasms / Q000556:secondary; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000473:pathology*; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000556:secondary; D051381:Rats; D011916:Rats, Inbred F344; D059016:Tumor Microenvironment