Mesenchymal stem cells promote colorectal cancer progression through AMPK/mTOR-mediated NF-κB activation.

Abstract

Mesenchymal stem cells (MSCs) exert a tumor-promoting effect in a variety of human cancers. This study was designed to identify the molecular mechanisms related to the tumor-promoting effect of MSCs in colorectal cancer. In vitro analysis of colorectal cancer cell lines cultured in MSC conditioned media (MSC-CM) showed that MSC-CM significantly promoted the progression of the cancer cells by enhancing cell proliferation, migration and colony formation. The tumorigenic effect of MSC-CM was attributed to altered expression of cell cycle regulatory proteins and inhibition of apoptosis. Furthermore, MSC-CM induced high level expression of a number of pluripotency factors in the cancer cells. ELISAs revealed MSC-CM contained higher levels of IL-6 and IL-8, which are associated with the progression of cancer. Moreover, MSC-CM downregulated AMPK mRNA and protein phosphorylation, but upregulated mTOR mRNA and protein phosphorylation. The NF-κB pathway was activated after addition of MSC-CM. An in vivo model in Balb/C mice confirmed the ability of MSC-CM to promote the invasion and proliferation of colorectal cancer cells. This study indicates that MSCs promote the progression of colorectal cancer via AMPK/mTOR-mediated NF-κB activation.

• Authors: Xiao-Bing Wu, Yang Liu, Gui-Hua Wang, Xiao Xu, Yang Cai, Hong-Yi Wang, Yan-Qi Li, Hong-Fang Meng, Fu Dai, Ji-De Jin
• Journal: Scientific reports (Sci Rep) Vol. 6 Pg. 21420 (Feb 19 2016) ISSN: 2045-2322 [Electronic] England
• PMID: 26892992 (Publication Type: Journal Article)

Chemical References

• Culture Media, Conditioned
• Cytokines
• NF-kappa B
• TOR Serine-Threonine Kinases
• AMP-Activated Protein Kinases

Topics

• AMP-Activated Protein Kinases (metabolism)
• Animals
• Apoptosis (drug effects)
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Cell Transformation, Neoplastic (genetics, metabolism)
• Colorectal Neoplasms (genetics, metabolism, pathology)
• Culture Media, Conditioned (pharmacology)
• Cytokines (metabolism)
• Disease Progression
• Enzyme Activation
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Male
• Mesenchymal Stem Cells (metabolism)
• Mice
• NF-kappa B (metabolism)
• Neoplastic Stem Cells (drug effects, metabolism)
• Signal Transduction (drug effects)
• TOR Serine-Threonine Kinases (metabolism)