In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 70, No. 8_Supplement ( 2010-04-15), p. 4255-4255
Abstract:
Background: Recently, mesenchymal stem cells (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 cells and the mechanisms underlying these effects remain unclear. We examined the role of MSCs in the tumor micro-environment using an orthotopic colon cancer model and a model of liver metastasis from colon cancer. Materials and Methods: Human MSCs labeled with fluorescent dye were injected into tail veins of nude mice bearing KM12SM human colon cancer cells. KM12SM cells alone or KM12SM cells mixed with MSCs were transplanted into the cecal wall or spleen of nude mice. Differentiation of MSCs in primary colon tumors and metastatic liver tumors were also analyzed. Migration assay and invasion assay were performed to examine attraction between KM12SM cells and MSCs in vitro. Results: 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 significantly greater tumor weight than did transplantation of KM12SM cells alone (p & lt; 0.05). The survival rate was significantly lower in the mixed-cell group, and liver metastasis was seen only in this group (p & lt; 0.001). Moreover, tumors resulting from transplantation of mixed cells had a significantly higher proliferating cell nuclear antigen labeling index (p & lt; 0.01), significantly greater microvessel area (p & lt; 0.01), and significantly lower apoptotic index (p & lt; 0.001). Splenic injection of KM12SM cells mixed with MSCs resulted in a significantly greater number of liver metastases than did splenic injection of KM12SM cells alone (p & lt; 0.01). 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 (p & lt; 0.05, respectively). Conclusion: MSCs migrate and differentiate into CAFs in tumor stroma, and they promote growth and metastasis of colon cancer by enhancing angiogenesis and by inhibiting apoptosis of tumor cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4255.
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM10-4255
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2010
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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