title: Paracrine factors from adipose-mesenchymal stem cells enhance metastatic capacity through Wnt signaling pathway in a colon cancer cell co-culture model.
abstract: BACKGROUND
  Mesenchymal stem cells (MSCs) in tumors have emerged as progenitors involved in stroma formation and metastasis of cancers, partially owing to their abilities to differentially express paracrine factors related to the proliferation and invasion of cancer cells. In this regard, increasing evidence has shown that MSCs have impacts on the malignancy of colon cancer, however, the underpinning mechanisms by which MSCs promote cancer metastasis remain elusive.
  
  
  METHODS
  To investigate the crosstalk between adipose-derived MSCs (AMSCs) isolated from adipose tissues and colon cancer cells, a co-culture transwell model of AMSCs and colon cancer cells was employed, and the activation of Wnt signaling and paracrine factors in colon cancer cells and AMSCs were measured.
  
  
  RESULTS
  The results showed that AMSCs could enhance the metastatic capacity of colon cancer cells with an elevated expression of mesenchymal-epithelial transition (EMT)-associated genes in a contact-dependent manner. Reciprocally, colon cancer cells were able to induce AMSCs to produce metastasis-related factors and cytokines, such as FGF10, VEGFC and matrix metalloproteinases (MMPs) in part through a mechanism of an activation of Wnt signaling, by which these factors in turn activate Wnt signaling of colon cancer cells. Intriguingly, an inhibition of Wnt signaling leads a reduced capacity of invasion and colony formation of colon cancer cells in vitro, and the tumorigenicity of cancer cells in a murine model.
  
  
  CONCLUSIONS
  These findings thus suggest that the crosstalk between the Wnt signaling of cancer cells and paracrine factors of AMSCs has an implication in colon cancer malignancy. This study thus uncovers a novel Wnt-paracrine factors mediated-crosstalk between colon cancer cells and AMSCs in cancer malignancy.
authors.affiliation: Institute of Human Stem Cell Research, the General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004 China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Chen
authors.affiliation: Institute of Human Stem Cell Research, the General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004 China.
authors.forename: Shudan
authors.initials: S
authors.lastname: Liu
authors.affiliation: Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Ningxia Medical University, Yinchuan, Ningxia, 750004 China.
authors.forename: Huiming
authors.initials: H
authors.lastname: Ma
authors.affiliation: Institute of Human Stem Cell Research, the General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004 China.
authors.forename: Xueyun
authors.initials: X
authors.lastname: Liang
authors.affiliation: Institute of Human Stem Cell Research, the General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004 China.
authors.forename: Haibin
authors.initials: H
authors.lastname: Ma
authors.affiliation: Institute of Human Stem Cell Research, the General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004 China.
authors.forename: Xiurui
authors.initials: X
authors.lastname: Yan
authors.affiliation: Department of Colorectal Surgery, the General Hospital of Ningxia Medical University, Yinchuan, 750004 China.
authors.forename: Bao
authors.initials: B
authors.lastname: Yang
authors.affiliation: Institute of Human Stem Cell Research, the General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004 China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wei
authors.affiliation: Institute of Human Stem Cell Research, the General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004 China.|Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in Western China, Ningxia University, Yinchuan, Ningxia, 750021 China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Liu
keywords: Adipose mesenchymal stem cells; Colon cancer; Malignancy; Paracrine factor; Wnt