%0 Journal Article
%T N-terminal and C-terminal heparin-binding domain polypeptides derived from fibronectin reduce adhesion and invasion of liver cancer cells
%A Nan-Hong Tang
%A Yan-Lin Chen
%A Xiao-Qian Wang
%A Xiu-Jin Li
%A Yong Wu
%A Qi-Lian Zou
%A Yuan-Zhong Chen
%J BMC Cancer
%D 2010
%I BioMed Central
%R 10.1186/1471-2407-10-552
%X The MHCC97H cells that adhered to FN in the presence of various concentrations of rhFNHN29 and rhFNHC36 polypeptides were stained with crystal violet and measured, and the effects of rhFNHN29 and rhFNHC36 on the invasion of the MHCC97H cells were then detected using the Matrigel invasion assay as well as a lung-metastasis mouse model. The expression level of integrins and focal adhesion kinase (FAK) phosphotyrosyl protein was examined by Western blot, and the activity of matrix metalloproteinases (MMPs) and activator protein 1 (AP-1) was analyzed by gelatin zymography and the electrophoretic mobility band-shift assay (EMSA), respectively.Both of the polypeptides rhFNHN29 and rhFNHC36 inhibited adhesion and invasion of MHCC97H cells; however, rhFNHC36 exhibited inhibition at a lower dose than rhFNHN29. These inhibitory effects were mediated by integrin ¦Áv¦Â3 and reversed by a protein tyrosine phosphatase inhibitor. Polypeptides rhFNHN29 and rhFNHC36 abrogated the tyrosine phosphorylation of focal adhesion kinase (p-FAK) and activation of activator protein 1 (AP-1), resulting in the decrease of integrin ¦Áv, ¦Â3 and ¦Â1 expression as well as the reduction of MMP-9 activity.Polypeptides rhFNHN29 and rhFNHC36 could potentially be applicable to human liver cancer as anti-adhesive and anti-invasive agents.Invasion and metastasis are important biological characteristics of malignant tumors. Metastatic formation requires specific cell-to-cell and cell-to-extracellular matrix (ECM) interactions mediated by integrins [1], cadherins [2], selectins [3], etc. In particular, integrin-mediated adhesion of tumor cells to ECM proteins and cell surface components is considered a crucial event in metastasis. Accordingly, the prevention of tumor cell adhesion to ECM proteins has been an area of interest as a potential target for therapeutic intervention [4-6].Fibronectin (FN) is a type of adhesive-attraction glycoprotein. Previous studies have shown that the anchoring of FN to ECM in vitro
%U http://www.biomedcentral.com/1471-2407/10/552