Differences in integrin expression and signaling within human breast cancer cells

Taherian, A.A. and Li, X. and Liu, Y. and Haas, T.A. (2011) Differences in integrin expression and signaling within human breast cancer cells. BMC Cancer, 11.

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Abstract

Background: Integrins are used as prognostic indicators in breast cancer. Following engagement with extracellular matrix proteins, their signaling influences numerous cellular processes including migration, proliferation, and death. Integrin signaling varies between cell types through differential expression of integrin subunits, and changes within a given cell upon exposure to a cell agonist or through changes in its surroundings. These variations in signaling can profoundly affect the phenotypic, tumorogenecity and metastatic properties of cancer cells. In the present study, we investigated if there were differences in the expression of integrins, integrin structures, and integrin co-receptors within three breast cancer cells and if these differences effected integrin signaling.Methods: Expression of integrins, urokinase receptor and vascular endothelial cell growth factor receptor (VEGFR) in metastatic MDA-MB-435 and MDA-MB-231, non-metastatic MCF7 and non-breast cancer Hek-293 cells was measured by flow cytometry. Cell adhesion was assessed using collagen, fibrinogen, fibronectin and vitronectin coated plates. Changes in kinase levels following PMA stimulation, and cell adhesion-induced activation of kinases were determined by western blot analysis. Distribution of actin stress fibers and focal adhesions was assessed by immunocytochemistry.Results: All cells expressed αvintegrins, while high β5and αvβ5expression was restricted to the cancer cells and high β3and αvβ3expression was restricted to MDA-MB-435 cells. The two metastatic cells were the least adhesive, but all cells adhered well to most proteins in the absence of PMA. All proliferating cells expressed activated pSrc, but only proliferating metastatic cells expressed high pMEK levels. PMA treatment resulted in time-dependent changes in activated kinase levels, and only MDA-MB-231 cells constitutively expressed high levels of activated pMEK. MDA-MB-435 cells formed more stress fibers and focal adhesions and only exhibited adhesion-induced activation of pMEK and pFAK. All cells expressed the urokinase receptor, but MCF7 cells had markedly higher VEGFR expression. Adhesion induced differential expression of pFAK, pMEK and pERK.Conclusions: This study demonstrates that breast cancers vary in their expression of integrins, their capacity to form focal adhesion and to signal through integrins. These differences likely contribute to phenotypic variations between cancer lines and account for some of the heterogeneity of breast cancer. © 2011 Taherian et al; licensee BioMed Central Ltd.

Item Type: Article
Additional Information: cited By 58
Uncontrolled Keywords: alpha5 integrin; alphaVbeta5 integrin; beta3 integrin; beta5 integrin; collagen; epidermal growth factor receptor 2; F actin; fibrinogen; focal adhesion kinase; integrin; mitogen activated protein kinase; phorbol 12 acetate 13 myristate; protein bcl 2; urokinase receptor; vasculotropin receptor; vitronectin; vitronectin receptor; alphaVbeta5 integrin; alphaVbeta6 integrin; beta3 integrin; integrin; phorbol 13 acetate 12 myristate; protein kinase; tumor antigen; tumor protein; urokinase receptor; vasculotropin receptor; vitronectin receptor, article; breast cancer; cancer cell; cell adhesion; cell proliferation; cell strain HEK293; cell strain MCF 7; controlled study; flow cytometry; focal adhesion; human; human cell; immunocytochemistry; MDA MB 231; MDA MB 435; phenotypic variation; protein expression; signal transduction; stress fiber; Western blotting; adenocarcinoma; biosynthesis; breast tumor; comparative study; drug effect; female; gene expression regulation; genetics; metabolism; pathology; physiology; signal transduction; tumor cell line; ultrastructure, Adenocarcinoma; Antigens, Neoplasm; Breast Neoplasms; Cell Adhesion; Cell Line, Tumor; Female; Focal Adhesions; Gene Expression Regulation, Neoplastic; HEK293 Cells; Humans; Integrin alphaVbeta3; Integrin beta3; Integrins; Neoplasm Proteins; Protein Kinases; Receptors, Urokinase Plasminogen Activator; Receptors, Vascular Endothelial Growth Factor; Receptors, Vitronectin; Signal Transduction; Stress Fibers; Tetradecanoylphorbol Acetate
Subjects: Biochemistry, Genetics and Molecular Biology
Divisions: Faculty of Medicine > Basic Sciences > Department of Pathology& Histology
Depositing User: editor . 2
Date Deposited: 27 Feb 2017 06:06
Last Modified: 05 Mar 2017 06:13
URI: http://eprints.kaums.ac.ir/id/eprint/848

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