title: 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.affiliation: Department of Gastroenterology, the Third Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230061, P. R. China.|Institute of Radiation Medicine, Academy Military Medical Sciences, Beijing 100850, P. R. China.
authors.forename: Xiao-Bing
authors.initials: XB
authors.lastname: Wu
authors.affiliation: The First Hospital Attached to Guiyang College of Traditional Chinese Medicine. Department of Clinical Laboratory, The First Hospital Attached to Guiyang College of Traditional Chinese Medicine, NO.71, Bao Shan North Road, Yunyan District, Guiyang City.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Institute of Radiation Medicine, Academy Military Medical Sciences, Beijing 100850, P. R. China.
authors.forename: Gui-Hua
authors.initials: GH
authors.lastname: Wang
authors.affiliation: The General Hospital of Chinese Armed Force Police, Beijing 100039, P. R. China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Xu
authors.affiliation: Institute of Radiation Medicine, Academy Military Medical Sciences, Beijing 100850, P. R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Institute of Radiation Medicine, Academy Military Medical Sciences, Beijing 100850, P. R. China.
authors.forename: Hong-Yi
authors.initials: HY
authors.lastname: Wang
authors.affiliation: Institute of Radiation Medicine, Academy Military Medical Sciences, Beijing 100850, P. R. China.
authors.forename: Yan-Qi
authors.initials: YQ
authors.lastname: Li
authors.affiliation: Institute of Radiation Medicine, Academy Military Medical Sciences, Beijing 100850, P. R. China.
authors.forename: Hong-Fang
authors.initials: HF
authors.lastname: Meng
authors.affiliation: Department of Gastroenterology, the Third Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230061, P. R. China.
authors.forename: Fu
authors.initials: F
authors.lastname: Dai
authors.affiliation: Institute of Radiation Medicine, Academy Military Medical Sciences, Beijing 100850, P. R. China.
authors.forename: Ji-De
authors.initials: JD
authors.lastname: Jin
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D018450:Disease Progression; D004789:Enzyme Activation; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D017077:Culture Media, Conditioned; D016207:Cytokines; D016328:NF-kappa B; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases