Journal Article

Differences in integrin expression and signaling within human breast cancer cells

Taherian, Aliakbar, Li, Xinlei, Liu, Yongqing, Haas, Thomas A

2011

Overview

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 α v integrins, while high β 5 and α v β 5 expression was restricted to the cancer cells and high β 3 and α v β 3 expression 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.

• Publisher: BioMed Central,BioMed Central Ltd,BMC
• Subject: Adenocarcinoma - metabolism / Adenocarcinoma - pathology / Antigens, Neoplasm - biosynthesis / Antigens, Neoplasm - genetics / Biomedical and Life Sciences / Biomedicine / Breast cancer / Breast Neoplasms - metabolism / Breast Neoplasms - pathology / Cancer Research / Care and treatment / Cell Adhesion / Cell and molecular biology / Cell Line, Tumor - drug effects / Cell Line, Tumor - metabolism / Cell Line, Tumor - ultrastructure / Development and progression / Female / Focal Adhesions / Gene expression / Gene Expression Regulation, Neoplastic - drug effects / Gene Expression Regulation, Neoplastic - physiology / Genetic aspects / Health Promotion and Disease Prevention / HEK293 Cells - metabolism / Humans / Integrin alphaVbeta3 - biosynthesis / Integrin alphaVbeta3 - genetics / Integrin beta3 - biosynthesis / Integrin beta3 - genetics / Integrins / Integrins - biosynthesis / Integrins - genetics / Integrins - physiology / Medicine/Public Health / Neoplasm Proteins - biosynthesis / Neoplasm Proteins - genetics / Neoplasm Proteins - physiology / Oncology / Physiological aspects / Protein Kinases - metabolism / Receptors, Urokinase Plasminogen Activator - biosynthesis / Receptors, Urokinase Plasminogen Activator - genetics / Receptors, Vascular Endothelial Growth Factor - biosynthesis / Receptors, Vascular Endothelial Growth Factor - genetics / Receptors, Vitronectin - biosynthesis / Receptors, Vitronectin - genetics / Research Article / Signal Transduction - drug effects / Stress Fibers - metabolism / Surgical Oncology / Tetradecanoylphorbol Acetate - pharmacology / Vascular endothelial growth factor