Mesenchymal Stromal Cells Promote Tumor Progression in Fibrosarcoma and Gastric Cancer Cells
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Background: Extensive evidence has accumulated regarding the role of mesenchymal stromal cells (MSCs) in tumor progression, but the exact effects and mechanisms underlying this role remain unclear. We investigated the effects of MSC-associated tumor progression in MSC-sarcoma models and a gastric cancer metastatic model. Methods: We conducted an in vitro growth kinetics assay and an in vivo tumor progression assay for sarcoma cells and gastric cancer cells in the presence or absence of MSCs. Results: MSC-cocultured human fibrosarcoma cells (HT1080) showed accelerated growth compared with HT1080 alone (79- vs 37-fold change, p<.050). For HT1080, human MSC-coinjected tumors showed significantly greater and highly infiltrative growth compared to those of HT1080 alone (p=.035). For mouse fibrosarcoma cells (WEHI164), mouse MSC-coinjected tumors had greater volume than those of WEHI164 alone (p=.141). For rat sarcoma cells (RR1022), rat MSC-coinjected tumors exhibited greater volume and infiltrative growth than those of RR1022 alone (p=.050). For human gastric cancer cells (5FU), tumors of 5FU alone were compact, nodular in shape, and expansile with good demarcation and no definite lung metastatic nodules, whereas tumors grown in the presence of human MSCs showed highly desmoplastic and infiltrative growth and multiple lung metastasis. Conclusions: We observed morphological evidence for MSC-associated tumor progression of fibrosarcomas and gastric cancer cells.
Abstract
Background: Extensive evidence has accumulated regarding the role of mesenchymal stromal cells (MSCs) in tumor progression, but the exact effects and mechanisms underlying this role remain unclear. We investigated the effects of MSC-associated tumor progression in MSC-sarcoma models and a gastric cancer metastatic model. Methods: We conducted an in vitro growth kinetics assay and an in vivo tumor progression assay for sarcoma cells and gastric cancer cells in the presence or absence of MSCs. Results: MSC-cocultured human fibrosarcoma cells (HT1080) showed accelerated growth compared with HT1080 alone (79- vs 37-fold change, p<.050). For HT1080, human MSC-coinjected tumors showed significantly greater and highly infiltrative growth compared to those of HT1080 alone (p=.035). For mouse fibrosarcoma cells (WEHI164), mouse MSC-coinjected tumors had greater volume than those of WEHI164 alone (p=.141). For rat sarcoma cells (RR1022), rat MSC-coinjected tumors exhibited greater volume and infiltrative growth than those of RR1022 alone (p=.050). For human gastric cancer cells (5FU), tumors of 5FU alone were compact, nodular in shape, and expansile with good demarcation and no definite lung metastatic nodules, whereas tumors grown in the presence of human MSCs showed highly desmoplastic and infiltrative growth and multiple lung metastasis. Conclusions: We observed morphological evidence for MSC-associated tumor progression of fibrosarcomas and gastric cancer cells.
참고문헌 (21)
- Artacho-Cordón A, "Tumor microenvironment and breast cancer progression: a complex scenario", Cancer Biol Ther, 13, pp.14~24 (2012)
- Kidd S, "Direct evidence of mesenchymal stem cell tropism for tumor and wounding microenvironments using in vivo bioluminescent imaging", Stem Cells, 27, pp.2614~2623 (2009)
- Klopp AH, "Concise review: dissecting a discrepancy in the literature: do mesenchymal stem cells support or suppress tumor growth?", Stem Cells, 29, pp.11~19 (2011)
- Karnoub AE, "Mesenchymal stem cells within tumour stroma promote breast cancer metastasis", Nature, 449, pp.557~563 (2007)
- Secchiero P, "Human bone marrow mesenchymal stem cells display anti-cancer activity in SCID mice bearing disseminated non-Hodgkin’s lymphoma xenografts", PLoS One, 5, pp.e11140~ (2010)
- Clarke MR, "Mesenchymal stem cells inhibit breast cancer cell migration and invasion through secretion of tissue inhibitor of metalloproteinase-1 and -2", Mol Carcinog (2014)[DOI]
- Shinagawa K, "Mesenchymal stem cells enhance growth and metastasis of colon cancer", Int J Cancer, 127, pp.2323~2333 (2010)
- Bissell MJ, "Why don’t we get more cancer? A proposed role of the microenvironment in restraining cancer progression", Nat Med, 17, pp.320~329 (2011)
- Tsukamoto S, "Mesenchymal stem cells promote tumor engraftment and metastatic colonization in rat osteosarcoma model", Int J Oncol, 40, pp.163~169 (2012)
- Xu WT, "Human mesenchymal stem cells (hMSCs) target osteosarcoma and promote its growth and pulmonary metastasis", Cancer Lett, 281, pp.32~41 (2009)
- Ottaviani G, "The etiology of osteosarcoma", Cancer Treat Res, 152, pp.15~32 (2009)
- Fox MG, "Osteosarcoma: review of the various types with emphasis on recent advancements in imaging", Semin Musculoskelet Radiol, 17, pp.123~136 (2013)
- Fletcher CD, "WHO classification of tumours of soft tissue and bone", pp.299~300 (2013), IARC Press
- Zhu H, "A protocol for isolation and culture of mesenchymal stem cells from mouse compact bone", Nat Protoc, 5, pp.550~560 (2010)
- Pereira C, "Hematopoietic colony-forming cell assays", Methods Mol Biol, 407, pp.177~208 (2007)
- Luu HH, "An orthotopic model of human osteosarcoma growth and spontaneous pulmonary metastasis", Clin Exp Metastasis, 22, pp.319~329 (2005)
- Koelzer VH, "The tumor border configuration of colorectal cancer as a histomorphological prognostic indicator", Front Oncol, 4, pp.29~ (2014)
- Cmielova J, "Gamma radiation induces senescence in human adult mesenchymal stem cells from bone marrow and periodontal ligaments", Int J Radiat Biol, 88, pp.393~404 (2012)
- Nicolay NH, "Mesenchymal stem cells retain their defining stem cell characteristics after exposure to ionizing radiation", Int J Radiat Oncol Biol Phys, 87, pp.1171~1178 (2013)
- Nomoto-Kojima N, "Interaction between adipose tissue stromal cells and gastric cancer cells in vitro", Cell Tissue Res, 344, pp.287~298 (2011)
- Martin J, "The role of sonic hedgehog reemergence during gastric cancer", Dig Dis Sci, 55, pp.1516~1524 (2010)