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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.
AuthorsShinji Tsukamoto, Kanya Honoki, Hiromasa Fujii, Yasuaki Tohma, Akira Kido, Toshio Mori, Toshifumi Tsujiuchi, Yasuhito Tanaka
JournalInternational journal of oncology (Int J Oncol) Vol. 40 Issue 1 Pg. 163-9 (Jan 2012) ISSN: 1791-2423 [Electronic] Greece
PMID21971610 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Topics
  • Animals
  • Bone Neoplasms (genetics, metabolism, pathology)
  • Cell Movement (physiology)
  • Gene Expression Profiling
  • Lung Neoplasms (secondary)
  • Mesenchymal Stem Cell Transplantation
  • Mesenchymal Stem Cells (metabolism, pathology)
  • Neoplasm Metastasis
  • Neoplasm Transplantation
  • Osteosarcoma (genetics, metabolism, pathology, secondary)
  • Rats
  • Rats, Inbred F344
  • Tumor Microenvironment

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