title: MIF, secreted by human hepatic sinusoidal endothelial cells, promotes chemotaxis and outgrowth of colorectal cancer in liver prometastasis.
abstract: Growth and invasion of metastatic colorectal cancer (CRC) cells in the liver depend on microenvironment. Here, we showed that human hepatic sinusoidal endothelial cells (HHSECs) induce chemotaxis and outgrowth of CRC cells. Macrophage migration inhibitory factor (MIF), released by HHSECs, stimulated chemotaxis of CRC cells. MIF secreted by HHSECs, but not by CRC cells themselves, promoted migration and epithelial-mesenchymal transition (EMT) and facilitated proliferation and apoptotic resistance of CRC cells. In orthotopic implantation models in nude mice, exogenous MIF stimulated growth of CRC cells and metastasis. Furthermore, MIF accelerated mobility of CRC cells by suppressing F-actin depolymerization and phosphorylating cofilin. Noteworthy, MIF levels were correlated with the size of hepatic metastases. We suggest that HHSECs and paracrine MIF promote initial migration and proliferation of CRC cells in the hepatic sinusoids to generate liver metastases.
authors.affiliation: Department of Pathology, Nanfang Hospital and School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.|Guangdong Provincial Key Laboratory of Molecular Tumor Pathology, Guangzhou 510515, China.
authors.forename: Chun-Ting
authors.initials: CT
authors.lastname: Hu
authors.affiliation: Department of Pathology, Nanfang Hospital and School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.|Guangdong Provincial Key Laboratory of Molecular Tumor Pathology, Guangzhou 510515, China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Guo
authors.affiliation: Department of Pathology, Nanfang Hospital and School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.|Guangdong Provincial Key Laboratory of Molecular Tumor Pathology, Guangzhou 510515, China.
authors.forename: Na
authors.initials: N
authors.lastname: Feng
authors.affiliation: Department of General Surgery, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200127, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Nanfang Hospital and School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
authors.forename: Na
authors.initials: N
authors.lastname: Zhou
authors.affiliation: Department of Pathology, Nanfang Hospital and School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Ma
authors.affiliation: Department of Pathology, Nanfang Hospital and School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Shen
authors.affiliation: Department of Pathology, Nanfang Hospital and School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
authors.forename: Gui-Hui
authors.initials: GH
authors.lastname: Tong
authors.affiliation: Department of Pathology, Nanfang Hospital and School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
authors.forename: Qian-Wen
authors.initials: QW
authors.lastname: Yan
authors.affiliation: Department of Pathology, Nanfang Hospital and School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
authors.forename: Shi-Jie
authors.initials: SJ
authors.lastname: Zhu
authors.affiliation: Department of Pathology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Xiu-Wu
authors.initials: XW
authors.lastname: Bian
authors.affiliation: Department of Pathology, School of Medical Sciences, Zhejiang University, Hangzhou 310006, China.
authors.forename: Mao D
authors.initials: MD
authors.lastname: Lai
authors.affiliation: Department of Pathology, Nanfang Hospital and School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.|Guangdong Provincial Key Laboratory of Molecular Tumor Pathology, Guangzhou 510515, China.
authors.forename: Yong-Jian
authors.initials: YJ
authors.lastname: Deng
authors.affiliation: Department of Pathology, Nanfang Hospital and School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.|Guangdong Provincial Key Laboratory of Molecular Tumor Pathology, Guangzhou 510515, China.
authors.forename: Yan-Qing
authors.initials: YQ
authors.lastname: Ding
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D002633:Chemotaxis; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D042783:Endothelial Cells / Q000378:metabolism*; D045325:HCT116 Cells; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000556:secondary*; D008263:Macrophage Migration-Inhibitory Factors / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D014162:Transfection
chemical_list: D008263:Macrophage Migration-Inhibitory Factors; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human
keywords: chemotaxis; colorectal cancer; hepatic sinusoidal endothelial cell; macrophage migration inhibitory factor; metastasis