title: Proteolysis of extracellular matrix by invadopodia facilitates human breast cancer cell invasion and is mediated by matrix metalloproteinases.
abstract: Breast cancer cell lines vary in invasive behavior and one highly invasive cell line (MDA-MB-231) proteolytically degrades extracellular matrix with invadopodia (Thompson et al. 1992, J Cell Physiol, 150, 534-44; Chen et al 1994, Breast Cancer Res Treat, 31, 217-26). Invadopodial proteolysis of extracellular matrix is thought to be necessary for invasion; however, this has not been demonstrated directly. To obtain such evidence, normal (HBL-100) and malignant (MCF-7, MDA-MB-231) breast cells were evaluated for invadopodial proteolysis of extracellular matrix and invasive behavior. We report that invadopodial proteolysis of immobilized fibronectin is positively correlated with invasion of cells into type I collagen gels. Moreover, reducing the proteolytic activity of invadopodia with the metalloproteinase inhibitor, batimastat (BB-94), also decreases invasion indicating that breast cancer cell invasion is dependent upon proteolytically active invadopodia.
authors.affiliation: Department of Pathology, Arkansas Cancer Research Center, University of Arkansas for Medical Sciences, Little Rock 72205-7199, USA. kellythomasj@exchange.uams.edu
authors.forename: T
authors.initials: T
authors.lastname: Kelly
authors.forename: Y
authors.initials: Y
authors.lastname: Yan
authors.forename: R L
authors.initials: RL
authors.lastname: Osborne
authors.forename: A B
authors.initials: AB
authors.lastname: Athota
authors.forename: T L
authors.initials: TL
authors.lastname: Rozypal
authors.forename: J C
authors.initials: JC
authors.lastname: Colclasure
authors.forename: W S
authors.initials: WS
authors.lastname: Chu
mesh_terms: D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D003094:Collagen / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005109:Extracellular Matrix / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000494:pharmacology; D011554:Pseudopodia / Q000378:metabolism; D013876:Thiophenes / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D004791:Enzyme Inhibitors; D005353:Fibronectins; D009363:Neoplasm Proteins; D013876:Thiophenes; D010649:Phenylalanine; D003094:Collagen; C080985:batimastat; D008666:Metalloendopeptidases