Endogenous Gastric-Resident Mesenchymal Stem Cells Contribute to Formation of Cancer Stroma and Progression of Gastric Cancer.
- Author:
Eun Kyung KIM
1
;
Hye Jung KIM
;
Young Il YANG
;
Jong Tae KIM
;
Min Young CHOI
;
Chang Soo CHOI
;
Kwang Hee KIM
;
Jeong Han LEE
;
Won Hee JANG
;
Soon Ho CHEONG
Author Information
1. Department of Pathology, Inje University School of Medicine, Busan, Korea. pathyang@inje.ac.kr
- Publication Type:In Vitro ; Original Article
- Keywords:
Gastric-resident mesenchymal stem cell;
Carcinoma-associated fibroblast;
Cancer stroma;
Stomach neoplasms
- MeSH:
Carcinogenesis;
Endothelial Cells;
Fibroblasts;
Heterografts;
Mesenchymal Stromal Cells*;
Organ Culture Techniques;
Plastics;
Stomach Neoplasms*;
Stromal Cells;
Transplantation, Heterologous
- From:Korean Journal of Pathology
2013;47(6):507-518
- CountryRepublic of Korea
- Language:English
-
Abstract:
BACKGROUND: Carcinoma-associated fibroblasts (CAFs) contribute to carcinogenesis and cancer progression, although their origin and role remain unclear. We recently identified and investigated the in situ identity and implications of gastric submucosa-resident mesenchymal stem cells (GS-MSCs) in the progression of gastric carcinogenesis. METHODS: We isolated GS-MSCs from gastric submucosa using hydrogel-supported organ culture and defined their identity. Isolated cells were assessed in vitro by immunophenotype and mesengenic multipotency. Reciprocal interactions between GS-MSCs and gastric cancer cells were evaluated. To determine the role of GS-MSCs, xenografts were constructed of gastric cancer cells admixed with or without GS-MSCs. RESULTS: Isolated cells fulfilled MSCs requirements in regard to plastic adherence, stromal cell immunophenotype, and multipotency. We demonstrated a paracrine loop that gastric cancer cells enhanced the migration, proliferation, and differentiation of GS-MSCs; additionally, GS-MSCs promoted the proliferation of gastric cancer cell in vitro. Xenograft experiments showed that GS-MSCs significantly promoted cancer growth and angiogenesis. GS-MSCs that integrated into gastric cancer became not only CAFs but also rarely endothelial cells which contributed to the formation of cellular and vascular cancer stroma. CONCLUSIONS: Endogenous GS-MSCs play an important role in gastric cancer progression.
