title: Endogenous gastric-resident mesenchymal stem cells contribute to formation of cancer stroma and progression of gastric cancer.
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.
authors.affiliation: Department of Pathology, Inje University School of Medicine, Busan, Korea.
authors.forename: Eun-Kyung
authors.initials: EK
authors.lastname: Kim
authors.affiliation: Department of Pathology, Inje University School of Medicine, Busan, Korea.
authors.forename: Hye-Jung
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Pathology, Inje University School of Medicine, Busan, Korea. ; Paik Institute for Clinical Research, Inje University School of Medicine, Busan, Korea.
authors.forename: Young-Il
authors.initials: YI
authors.lastname: Yang
authors.affiliation: Paik Institute for Clinical Research, Inje University School of Medicine, Busan, Korea.
authors.forename: Jong Tae
authors.initials: JT
authors.lastname: Kim
authors.affiliation: Paik Institute for Clinical Research, Inje University School of Medicine, Busan, Korea.
authors.forename: Min-Young
authors.initials: MY
authors.lastname: Choi
authors.affiliation: Department of Surgery, Inje University School of Medicine, Busan, Korea.
authors.forename: Chang Soo
authors.initials: CS
authors.lastname: Choi
authors.affiliation: Department of Surgery, Inje University School of Medicine, Busan, Korea.
authors.forename: Kwang-Hee
authors.initials: KH
authors.lastname: Kim
authors.affiliation: Paik Institute for Clinical Research, Inje University School of Medicine, Busan, Korea. ; Department of Anesthesiology, Inje University School of Medicine, Busan, Korea.
authors.forename: Jeong-Han
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Paik Institute for Clinical Research, Inje University School of Medicine, Busan, Korea.
authors.forename: Won-Hee
authors.initials: WH
authors.lastname: Jang
authors.affiliation: Paik Institute for Clinical Research, Inje University School of Medicine, Busan, Korea. ; Department of Anesthesiology, Inje University School of Medicine, Busan, Korea.
authors.forename: Soon-Ho
authors.initials: SH
authors.lastname: Cheong
keywords: Cancer stroma; Carcinoma-associated fibroblast; Gastric-resident mesenchymal stem cell; Stomach neoplasms