Endogenous Gastric-Resident Mesenchymal Stem Cells Contribute to Formation of Cancer Stroma and Progression of Gastric Cancer
김은경, 김혜정, 양영일, 김종태, 최민영, 최창수, 김광희, 이정한, 장원희, 정순호,
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김은경 ( Kim Eun-Kyung )
Inje University College of Medicine Department of Pathology
김혜정 ( Kim Hye-Jung )
Inje University College of Medicine Department of Pathology
양영일 ( Yang Young-Il )
Inje University College of Medicine Department of Pathology
김종태 ( Kim Jong-Tae )
Inje University Paik Institute for Clinical Research
최민영 ( Choi Min-Young )
Inje University Paik Institute for Clinical Research
최창수 ( Choi Chang-Soo )
Inje University College of Medicine Department of Surgery
김광희 ( Kim Kwang-Hee )
Inje University College of Medicine Department of Surgery
이정한 ( Lee Jeong-Han )
Inje University Paik Institute for Clinical Research
장원희 ( Jang Won-Hee )
Inje University Paik Institute for Clinical Research
정순호 ( Cheong Soon-Ho )
Inje University Paik Institute for Clinical Research
KMID : 0357920130470060507
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 (GSMSCs) 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 GSMSCs 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.
키워드
Gastric-resident mesenchymal stem cell; Carcinoma-associated fibroblast; Cancer stroma; Stomach neoplasms
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