Cited by 244Mesenchymal stem cell researchAngiogenesis and VEGF in CancerCancer Cells and Metastasis

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Mesenchymal Stromal Cells Promote Tumor Growth through the Enhancement of Neovascularization

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Suzuki, Kazuhiro, Sun, Ruowen, Origuchi, Makoto, Kanehira, Masahiko, Takahata, Takenori, Itoh, Jugoh, Umezawa, Akihiro, Kijima, Hiroshi, Fukuda, Shinsaku, Saijo, Yasuo·2011·Molecular Medicine

DOI 10.2119/molmed.2010.00157PMC PMC3146617

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Abstract

Mesenchymal stromal cells (MSCs), also called mesenchymal stem cells, migrate and function as stromal cells in tumor tissues. The effects of MSCs on tumor growth are controversial. In this study, we showed that MSCs increase proliferation of tumor cells in vitro and promote tumor growth in vivo. We also further analyzed the mechanisms that underlie these effects. For use in in vitro and in vivo experiments, we established a bone marrow-derived mesenchymal stromal cell line from cells isolated in C57BL/6 mice. Effects of murine MSCs on tumor cell proliferation in vitro were analyzed in a coculture model with B16-LacZ cells. Both coculture with MSCs and treatment with MSC-conditioned media led to enhanced growth of B16-LacZ cells, although the magnitude of growth stimulation in cocultured cells was greater than that of cells treated with conditioned media. Co-injection of B16-LacZ cells and MSCs into syngeneic mice led to increased tumor size compared with injection of B16-LacZ cells alone. Identical experiments using Lewis lung carcinoma (LLC) cells instead of B16-LacZ cells yielded similar results. Consistent with a role for neovascularization in MSC-mediated tumor growth, tumor vessel area was greater in tumors resulting from co-injection of B16-LacZ cells or LLCs with MSCs than in tumors induced by injection of cancer cells alone. Co-injected MSCs directly supported the tumor vasculature by localizing close to vascular walls and by expressing an endothelial marker. Furthermore, secretion of leukemia inhibitory factor, macrophage colony-stimulating factor, macrophage inflammatory protein-2 and vascular endothelial growth factor was increased in cocultures of MSCs and B16-LacZ cells compared with B16-LacZ cells alone. Together, these results indicate that MSCs promote tumor growth both in vitro and in vivo and suggest that tumor promotion in vivo may be attributable in part to enhanced angiogenesis.

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Authors: Suzuki, K., Sun, R., Origuchi, M., Kanehira, M., Takahata, T., Itoh, J., Umezawa, A., Kijima, H., Fukuda, S., & Saijo, Y.
Affiliations: Hirosaki University (JP)
Tohoku University (JP)
National Center For Child Health and Development (JP)
Corresponding author: Saijo, Yasuo
ORCID: Suzuki, Kazuhiro
Kanehira, Masahiko
Umezawa, Akihiro
Kijima, Hiroshi
Fukuda, Shinsaku
Saijo, Yasuo
Venue: Molecular Medicine
Publisher: Springer Science and Business Media LLC
Published: 2011-03-11
Volume: 17
Issue: 7-8
Pages: 579-587
ISSN: 1076-1551 (ISSN-L)
1528-3658
DOI: 10.2119/molmed.2010.00157
PMC: PMC3146617
OpenAlex: W2207758069
Cited by: 244
References: 38
Citations by year: 2026: 6 · 2025: 12 · 2024: 11 · 2023: 10 · 2022: 12 · 2021: 17 · 2020: 24 · 2019: 19 · 2018: 25 · 2017: 14 · 2016: 25 · 2015: 16 · 2014: 21 · 2013: 12 · 2012: 17
FWCI: 8.44
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
Locations: Molecular Medicine (publishedVersion, cc-by)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Japan Society for the Promotion of Science (16022206, 20390229, 23790895, 22659160)
RIKEN
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
Keywords: mesenchymal stem cells, tumor growth, tumor angiogenesis, angiogenesis, tumor cell proliferation, bone marrow-derived stromal cells, Lewis lung carcinoma, leukemia inhibitory factor, macrophage colony-stimulating factor, CXCL2, vascular endothelial growth factor, tumor vasculature
MeSH terms: Animals, Cells, Cultured, Female, Flow Cytometry, Mice, Transgenic, Neoplasm Transplantation, Neoplasms, Experimental, Neovascularization, Pathologic, Macrophage Colony-Stimulating Factor, Microscopy, Confocal, Coculture Techniques, Antigens, CD34, Vascular Endothelial Growth Factor A, Mesenchymal Stem Cell Transplantation, Cell Line, Tumor, Tumor Burden, Cell Proliferation, Green Fluorescent Proteins, Mice, Chemokine CXCL2, Mesenchymal Stem Cells

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Mesenchymal Stromal Cells Promote Tumor Growth through the Enhancement of Neovascularization

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