Mesenchymal stem cells enhance growth and metastasis of colon cancer
Abstract
Recently, mesenchymal stem cells (MSCs) were reported to migrate to tumor stroma as well as injured tissue. We examined the role of human MSCs in tumor stroma using an orthotopic nude mice model of KM12SM colon cancer. In in vivo experiments, systemically injected MSCs migrated to the stroma of orthotopic colon tumors and metastatic liver tumors. Orthotopic transplantation of KM12SM cells mixed with MSCs resulted in greater tumor weight than did transplantation of KM12SM cells alone. The survival rate was significantly lower in the mixed‐cell group, and liver metastasis was seen only in this group. Moreover, tumors resulting from transplantation of mixed cells had a significantly higher proliferating cell nuclear antigen labeling index, significantly greater microvessel area and significantly lower apoptotic index. Splenic injection of KM12SM cells mixed with MSCs, in comparison to splenic injection of KM12SM cells alone, resulted in a significantly greater number of liver metastases. MSCs incorporated into the stroma of primary and metastatic tumors expressed α‐smooth muscle actin and platelet‐derived growth factor receptor‐β as carcinoma‐associated fibroblast (CAF) markers. In in vitro experiments, KM12SM cells recruited MSCs, and MSCs stimulated migration and invasion of tumor cells through the release of soluble factors. Collectively, MSCs migrate and differentiate into CAFs in tumor stroma, and they promote growth and metastasis of colon cancer by enhancing angiogenesis, migration and invasion and by inhibiting apoptosis of tumor cells.
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The use of MSCs themselves may contribute to tumor growth given reports of their predisposition to differentiate into cancer-associated fibroblasts, which are correlated with tumor growth, invasion and metastasis.
“The use of MSCs themselves may also have a contribution given the reports of their predisposition to differentiate into cancer-associated fibroblasts, which are correlated with tumor growth, invasion and metastasis [102], [103].”
From Mesenchymal stem cell secretome for regenerative medicine: Where do we stand? (2025) · cites this paper as [103]
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“Tumor tissue contains abundant growth factors, cytokines and matrix-remodeling proteins, explaining why tumors are likened to wounds that never heal.(4) MSCs are reported to migrate to tumor sites as well as sites of injury and to incorporate into tumor stroma, but the effects of interactions between MSCs and tumor ce…”
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- Authors
- Shinagawa, K., Kitadai, Y., Tanaka, M., Sumida, T., Kodama, M., Higashi, Y., Tanaka, S., Yasui, W., & Chayama, K.
- Affiliations
- Hiroshima University (JP)
- Hiroshima University Hospital (JP)
- Corresponding author
- Kitadai, Yasuhiko
- Venue
- International Journal of Cancer
- Publisher
- Wiley
- Published
- 2010-05-06
- Volume
- 127
- Issue
- 10
- Pages
- 2323-2333
- ISSN
- 0020-7136 (ISSN-L)
- 1097-0215
- OpenAlex
- W2136497698
- Cited by
- 308
- References
- 6
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 13 · 2023: 11 · 2022: 20 · 2021: 17 · 2020: 18 · 2019: 17 · 2018: 21 · 2017: 18 · 2016: 24 · 2015: 28 · 2014: 27 · 2013: 42 · 2012: 21
- FWCI
- 12.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- International Journal of Cancer (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Keywords
- mesenchymal stem cells, colon cancer, liver metastasis, tumor stroma, cancer-associated fibroblasts, tumor microenvironment, angiogenesis, tumor cell migration and invasion, apoptosis, orthotopic xenograft, PDGFRβ, alpha-smooth muscle actin
- MeSH terms
- Animals, Cell Differentiation, Cell Movement, Colonic Neoplasms, Female, Humans, Liver Neoplasms, Mice, Inbred BALB C, Stromal Cells, Mesenchymal Stem Cell Transplantation, Cell Growth Processes, Mice, Mesenchymal Stem Cells
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