Gastric cancer-derived MSC-secreted PDGF-DD promotes gastric cancer progression

Purpose: This study was designed to investigate the role of PDGF-DD secreted by gastric cancer-derived mesenchymal stem cells (GC-MSCs) in human gastric Cancer progression.

Methods: Gastric Cancer cells were indirectly co-cultured with GC-MSCs in a transwell system. The growth and migration of gastric Cancer cells were evaluated by cell colony formation assay and transwell migration assay, respectively. The production of PDGF-DD in GC-MSCs was determined by using Luminex and ELISA. Neutralization of PDGFR-β by su16f and siRNA interference of PDGF-DD in GC-MSCs was used to demonstrate the role of PDGF-DD produced by GC-MSCs in gastric Cancer progression.

Results: GC-MSC conditioned medium promoted gastric Cancer cell proliferation and migration in vitro and in vivo. Co-culture with GC-MSCs increased the phosphorylation of PDGFR-β in SGC-7901 cells. Neutralization of PDGFR-β by su16f blocked the promoting role of GC-MSC conditioned medium in gastric Cancer cell proliferation and migration. Recombinant PDGF-DD duplicated the effects of GC-MSC conditioned medium on gastric Cancer cells. Knockdown of PDGF-DD in GC-MSCs abolished its effects on gastric Cancer cells in vitro and in vivo.

Conclusions: PDGF-DD secreted by GC-MSCs is capable of promoting gastric Cancer cell progression in vitro and in vivo. Targeting the PDGF-DD/PDGFR-β interaction between MSCs and gastric Cancer cells may represent a novel strategy for gastric Cancer therapy.