title: β1 integrin is required for anchorage-independent growth and invasion of tumor cells in a context dependent manner.
abstract: Recent studies suggest that extracellular matrix (ECM) components within the tumor microenvironment can influence malignant progression, thus we investigated the influence of the ECM binding receptor β1 integrin, on the hallmark properties of tumorigenesis. Small interfering (si) or short hairpin (sh) RNA approaches were used to deplete β1 integrin in cancer cell lines. β1 integrin-depleted cells were then assessed for their growth and invasive capabilities using 2-dimensional (2D) or 3D culture conditions. Depletion of β1 integrin expression did not impact cell growth in 2D assay systems; however, β1 integrin and its ligand fibronectin were required for growth in 3D. β1 integrin-depleted cells also had reduced invasive capabilities, in part due to increased tissue inhibitor of metalloprotease (TIMP)-2 expression in conjunction with down-regulation of matrix metalloprotease (MMP)-9 levels in β1 integrin-depleted cells. Our results suggest that despite no apparent effect on 2D cell growth, fibronectin-β1 integrin signaling is a critical mediator of the 3D growth and invasive properties of tumor cells. These observations highlight the importance of investigating the role of adhesion molecules in the appropriate context and furthermore identify β1 integrin as a possible therapeutic target to inhibit the aggressive growth and invasion of tumor cells.
authors.affiliation: Cancer Therapeutics Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada. allana.schooley@gmail.com
authors.forename: Allana M
authors.initials: AM
authors.lastname: Schooley
authors.forename: Natalie M
authors.initials: NM
authors.lastname: Andrews
authors.forename: Huijun
authors.initials: H
authors.lastname: Zhao
authors.forename: Christina L
authors.initials: CL
authors.lastname: Addison
mesh_terms: D002448:Cell Adhesion / Q000502:physiology; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D015398:Signal Transduction; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis; D014162:Transfection
chemical_list: D005353:Fibronectins; D019012:Integrin beta1; D034741:RNA, Small Interfering; D019716:Tissue Inhibitor of Metalloproteinase-2; D020780:Matrix Metalloproteinase 9