title: Epidermal growth factor receptor targeting alters gene expression and restores the adhesion function of cancerous cells as measured by single cell force spectroscopy.
abstract: Loss of cell-cell adhesion function is a common characteristic of many human epithelial carcinomas that is frequently due to loss of E-cadherin expression. In cancer progression, loss of E-cadherin is associated with invasion and metastasis potential, hence restoration of its function may contribute to the metastasis inhibition. This study examined effect of Epidermal Growth Factor Receptor (EGFR/Her1) blockade on the E-cadherin expression, cellular adherence, and cell elasticity in two human epithelial cancer cell lines, MCF7 and A431. EGFR blocking agents as antibodies or small molecules target EGFR directly. Furthermore, due to intracellular signaling pathways they influence cell behavior and activities. The idea here is to investigate the effect of reduced activity of this signaling pathway using anti-EGFR Antibody (Cetuximab) and tyrosine kinase inhibitor (Lapatinib) on cell-cell adhesion and cell mechanical properties. Real-Time PCR analysis demonstrated that treatment of cells with considered drugs increased the expression of E-cadherin gene among samples. The atomic force microscopy-based single cell force spectroscopy technique was used to measure adhesive force of cancerous cells. Results indicated that inhibition of EGFR activity elevated cell-cell adhesion force, accompanied by stiffening of the cell bodies. In summary, Cetuximab and Lapatinib have been found to mediate cell-cell adhesion by restoration of E-cadherin expression and function. Our data suggest possible therapeutic potential for inhibition of metastasis via the blockade of EGFR signaling.
authors.affiliation: Faculty of Biomedical Engineering, Amirkabir University of Technology (Tehran Polytechnic), No. 424, Hafez Avenue, Tehran, P.O. Box 15875-4413, Iran.
authors.forename: Shohreh
authors.initials: S
authors.lastname: Azadi
authors.affiliation: Faculty of Biomedical Engineering, Amirkabir University of Technology (Tehran Polytechnic), No. 424, Hafez Avenue, Tehran, P.O. Box 15875-4413, Iran. tafazoli@aut.ac.ir.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Tafazzoli-Shadpour
authors.affiliation: Faculty of Biology, Albert-Ludwigs-University Freiburg, Schänzlestraße 1, 79104, Freiburg, Germany.|Centre for Biological Signalling Studies (BIOSS), Albert-Ludwigs-University Freiburg, Schänzlestraße 18, 79104, Freiburg, Germany.|Freiburg Center for Interactive Materials and Bioinspired Technology (FIT), Albert-Ludwigs-University Freiburg, Georges-Köhler-Allee 105, 79110, Freiburg, Germany.
authors.forename: Ramin
authors.initials: R
authors.lastname: Omidvar
authors.affiliation: Tissue Engineering and Applied Cell Sciences Department, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Lida
authors.initials: L
authors.lastname: Moradi
authors.affiliation: National Cell Bank of Iran, Pasteur Institute of Iran, Pasteur Avenue, P.O. Box 13164, Tehran, Iran. habibi_m@pasteur.ac.ir.
authors.forename: Mahdi
authors.initials: M
authors.lastname: Habibi-Anbouhi
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000648:ultrastructure; D002448:Cell Adhesion / Q000187:drug effects; D000068818:Cetuximab / Q000494:pharmacology*; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D000077341:Lapatinib; D061986:MCF-7 Cells; D018625:Microscopy, Atomic Force; D009363:Neoplasm Proteins / Q000378:metabolism*; D011799:Quinazolines / Q000494:pharmacology*
chemical_list: D009363:Neoplasm Proteins; D011799:Quinazolines; D000077341:Lapatinib; C512478:EGFR protein, human; D066246:ErbB Receptors; D000068818:Cetuximab
keywords: Atomic force microscopy; Epithelial cadherin; Metastasis; Monoclonal antibody; Small molecule; Young’s modulus