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Integrin alpha(v)beta3 expression confers on tumor cells a greater propensity to metastasize to bone.
Pecheur, Isabelle; Peyruchaud, Olivier; Serre, Claire-Marie et al.
2002In FASEB Journal, 16 (10), p. 1266-8
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Keywords :
Animals; Bone Neoplasms/metabolism/pathology/secondary; Breast Neoplasms/metabolism/pathology; CHO Cells; Carcinoma/metabolism/pathology/secondary; Cell Adhesion; Cell Division; Cell Movement; Collagen/metabolism; Cricetinae; Female; Integrin-Binding Sialoprotein; Mice; Mice, Nude; Models, Biological; Neoplasm Invasiveness; Receptors, Vitronectin/genetics/metabolism/physiology; Sialoglycoproteins/metabolism; Transfection; Tumor Cells, Cultured
Abstract :
[en] 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.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Pecheur, Isabelle
Peyruchaud, Olivier
Serre, Claire-Marie
Guglielmi, Julien
Voland, Carole
Bourre, Francois
Margue, Christiane  ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Cohen-Solal, Martine
Buffet, Annie
Kieffer, Nelly
Clezardin, Philippe
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Title :
Integrin alpha(v)beta3 expression confers on tumor cells a greater propensity to metastasize to bone.
Publication date :
Journal title :
FASEB Journal
Publisher :
Federation of American Societies for Experimental Biology, United States - Maryland
Volume :
Issue :
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Peer reviewed :
Peer Reviewed verified by ORBi
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