Mesenchymal stem cells (MSCs) extensively interact with
cancer cells and other stroma cells in the tumor microenvironment. However, the role of MSCs in
colorectal cancer (CRC) progression and
metastasis is controversial. This study was designed to identify the role of
inflammation-activated-MSCs in CRC development. Our results show that
tumor necrosis factor (TNF)-α-preactivated-hMSCs significantly promote the progression of
colon cancer cells by enhancing cell proliferation, epithelial-mesenchymal transition, migration, and invasion. TNF-α-primed-hMSCs secrete high level of CCL5, which interacts with its
receptor CCR1 expressed in
colon cancer cells. Interestingly, the stimulation of
colon cancer cell progression by TNF-α-primed hMSCs is associated with the upregulation of β-
catenin signaling pathway. Blocking β-
catenin pathway significantly decreases the TNF-α-primed-
conditioned medium or CCL5-mediated
cancer cell progression by decreasing the enhancement of Slug, suggesting that the CCL5/β-
catenin/Slug pathway plays a critical role in hMSC-mediated
cancer progression. Furthermore, in vivo model in nude mice confirms the ability of hMSCs to promote the proliferation and progression of
colon cancer cells, and the upregulation of CCl5/β-
catenin/Slug pathway. Taken together, the present study has demonstrated a novel pathway involving CCl5/CCR1/β-
catenin/Slug, via which hMSCs promotes CRC development.