MIF, secreted by human hepatic sinusoidal endothelial cells, promotes chemotaxis and outgrowth of colorectal cancer in liver prometastasis

نویسندگان

  • Chun-Ting Hu
  • Li-Li Guo
  • Na Feng
  • Lei Zhang
  • Na Zhou
  • Li-Li Ma
  • Lan Shen
  • Gui-Hui Tong
  • Qian-Wen Yan
  • Shi-Jie Zhu
  • Xiu-Wu Bian
  • Mao-De Lai
  • Yong-Jian Deng
  • Yan-Qing Ding
چکیده

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.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Hypoxia-induced endothelial secretion of macrophage migration inhibitory factor and role in endothelial progenitor cell recruitment

Macrophage migration inhibitory factor (MIF) is a pleiotropic inflammatory cytokine that was recently identified as a non-cognate ligand of the CXC-family chemokine receptors 2 and 4 (CXCR2 and CXCR4). MIF is expressed and secreted from endothelial cells (ECs) following atherogenic stimulation, exhibits chemokine-like properties and promotes the recruitment of leucocytes to atherogenic endothel...

متن کامل

Ephrin B2/EphB4 pathway in hepatic stellate cells stimulates Erk-dependent VEGF production and sinusoidal endothelial cell recruitment.

Chemotaxis signals between hepatic stellate cells (HSC) and sinusoidal endothelial cells (SEC) maintain hepatic vascular homeostasis and integrity and also regulate changes in sinusoidal structure in response to liver injury. Our prior studies have demonstrated that the bidirectional chemotactic signaling molecules EphrinB2 and EphB4 are expressed in HSC. The aim of our present study was to exp...

متن کامل

Conditioned Medium from Cultured Colorectal Cancer Cells Affects Peripheral Blood Mononuclear Cells Inflammatory Phenotype in Vitro

Background: Colorectal cancer (CRC) is the third most common cancer worldwide. Studies have indicated that immune cells and soluble factors play a key role in maintaining the balance between tumor-promoting inflammation and anti-tumor immunity. It has been shown that secreted cytokines from CRC cell lines could affect peripheral blood mononuclear cells (PBMCs), monocytes, and macrophages phenot...

متن کامل

Regulation by vascular endothelial growth factor of human colon cancer tumorigenesis in a mouse model of experimental liver metastasis.

To investigate the relationship between angiogenesis and hepatic tumorigenesis, we examined the expression of vascular endothelial growth factor (VEGF) in 8 human colon carcinoma cell lines and in 30 human colorectal cancer liver metastases. Abundant message for VEGF was found in all tumors, localized to the malignant cells within each neoplasm. Two receptors for VEGF, KDR and flt1, were also d...

متن کامل

Expression of Endoderm and Hepatic Specific Genes after in vitro Differentiation of Human Embryonic Stem Cells

Background: Human embryonic stem cells (hESC), which are derived from the inner cell mass of the blastocysts, have been considered to be pluripotent cells. In this study we examine the differentiating potential of hESC into hepatocytes by characterization of the expression of endoderm and liver-specific genes. Methods: hESC were cultivated in suspension to form aggregates, the embryoid bodies. ...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 6  شماره 

صفحات  -

تاریخ انتشار 2015