title: Integrin alpha(v)beta3 expression confers on tumor cells a greater propensity to metastasize to bone.
abstract: The reasons why tumor cells metastasize to bone remain obscure. There is some evidence to support the theory that integrins (acting as cell surface adhesion receptors) play a role in mediating metastasis in certain organs. Here, we report that overexpression of a functionally active integrin alpha(v)b3 in Chinese hamster ovary (CHO) tumor cells drastically increased the incidence, number, and area of bone metastases in nude mice compared with those observed in mock-transfected CHO cells (CHO dhfr+) or in CHO cells expressing a functionally inactive integrin alpha(v)b3 (CHO beta3Delta744). Moreover, a breast cancer cell line (B02) established from bone metastases caused by MDA-MB-231 cells constitutively overexpressed integrin alpha(v)b3, whereas the cell surface expression level of other integrins remained unchanged. In vivo, the extent of bone metastases in B02-bearing mice was significantly increased compared with that of MDA-MB-231-bearing mice. In vitro, B02 cells and CHO cells expressing a functionally active integrin alpha(v)b3 exhibited substantially increased invasion of and adhesion to mineralized bone, bone sialoprotein, and collagen compared with those found with MDA-MB-231, CHO dhfr+, and CHO beta3Delta744 cells, respectively. Overall, our findings suggest that integrin alpha(v)b3 expression in tumor cells accelerates the development of osteolytic lesions, presumably through increased invasion of and adhesion to bone.
authors.affiliation: INSERM Research Unit 403, Faculty of Medicine Laënnec, Lyon, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Pécheur
authors.forename: Olivier
authors.initials: O
authors.lastname: Peyruchaud
authors.forename: Claire-Marie
authors.initials: CM
authors.lastname: Serre
authors.forename: Julien
authors.initials: J
authors.lastname: Guglielmi
authors.forename: Carole
authors.initials: C
authors.lastname: Voland
authors.forename: Francois
authors.initials: F
authors.lastname: Bourre
authors.forename: Christiane
authors.initials: C
authors.lastname: Margue
authors.forename: Martine
authors.initials: M
authors.lastname: Cohen-Solal
authors.forename: Annie
authors.initials: A
authors.lastname: Buffet
authors.forename: Nelly
authors.initials: N
authors.lastname: Kieffer
authors.forename: Philippe
authors.initials: P
authors.lastname: Clézardin
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology / Q000556:secondary*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D016466:CHO Cells; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology / Q000556:secondary; D002448:Cell Adhesion; D002455:Cell Division; D002465:Cell Movement; D003094:Collagen / Q000378:metabolism; D006224:Cricetinae; D005260:Female; D058574:Integrin-Binding Sialoprotein; D051379:Mice; D008819:Mice, Nude; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D019030:Receptors, Vitronectin / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D012795:Sialoglycoproteins / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: C546872:Ibsp protein, mouse; D058574:Integrin-Binding Sialoprotein; D019030:Receptors, Vitronectin; D012795:Sialoglycoproteins; D003094:Collagen