Korean J Pathol.  2013 Dec;47(6):507-518.

Endogenous Gastric-Resident Mesenchymal Stem Cells Contribute to Formation of Cancer Stroma and Progression of Gastric Cancer

• Kim EK
• Kim HJ
• Yang YI
• Kim JT
• Choi MY
• Choi CS
• Kim KH
• Lee JH
• Jang WH
• Cheong SH

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.

Keyword

Gastric-resident mesenchymal stem cell; Carcinoma-associated fibroblast; Cancer stroma; Stomach neoplasms

MeSH Terms

Carcinogenesis
Endothelial Cells
Fibroblasts
Heterografts
Mesenchymal Stromal Cells*
Organ Culture Techniques
Plastics
Stomach Neoplasms*
Stromal Cells
Transplantation, Heterologous
Plastics