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Integrin αvβ3 expression confers on tumor cells a greater propensity to metastasize to bone
Author(s) -
Pecheur Isabelle,
Peyruchaud Olivier,
Serre ClaireMarie,
Guglielmi Julien,
Voland Carole,
Bourre Francois,
Margue Christiane,
CohenSolal Martine,
Buffet Annie,
Kieffer Nelly,
CléZardin Philippe
Publication year - 2002
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.01-0911fje
Subject(s) - integrin , chinese hamster ovary cell , collagen receptor , bone metastasis , bone sialoprotein , chemistry , cancer research , cell culture , transfection , cell adhesion , microbiology and biotechnology , cell , biology , metastasis , receptor , cancer , medicine , osteocalcin , biochemistry , alkaline phosphatase , enzyme , genetics
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 αvβ3 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 αvβ3 (CHO β3∆744). Moreover, a breast cancer cell line (B02) established from bone metastases caused by MDA‐MB‐231 cells constitutively overexpressed integrin αvβ3, 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 MDAMB‐231‐bearing mice. In vitro, B02 cells and CHO cells expressing a functionally active integrin αvβ3 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 β3∆744 cells, respectively. Overall, our findings suggest that integrin αvβ3 expression in tumor cells accelerates the development of osteolytic lesions, presumably through increased invasion of and adhesion to bone.