Pécheur Isabelle, Peyruchaud Olivier, Serre Claire-Marie, Guglielmi Julien, Voland Carole, Bourre Francois, Margue Christiane, Cohen-Solal Martine, Buffet Annie, Kieffer Nelly, Clézardin Philippe
INSERM Research Unit 403, Faculty of Medicine Laënnec, Lyon, France.
FASEB J. 2002 Aug;16(10):1266-8. doi: 10.1096/fj.01-0911fje. Epub 2002 Jun 21.
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.
肿瘤细胞转移至骨的原因仍不清楚。有一些证据支持整合素（作为细胞表面黏附受体）在某些器官介导转移中发挥作用这一理论。在此，我们报告，与mock转染的中国仓鼠卵巢（CHO）细胞（CHO dhfr+）或表达功能失活的整合素α(v)β3的CHO细胞（CHO β3Delta744）相比，在中国仓鼠卵巢肿瘤细胞中过表达功能活性整合素α(v)β3会显著增加裸鼠骨转移的发生率、数量和面积。此外，由MDA-MB-231细胞引起的骨转移所建立的乳腺癌细胞系（B02）持续过表达整合素α(v)β3，而其他整合素的细胞表面表达水平保持不变。在体内，与携带MDA-MB-231的小鼠相比，携带B02的小鼠骨转移程度显著增加。在体外，与MDA-MB-231、CHO dhfr+和CHO β3Delta744细胞相比，表达功能活性整合素α(v)β3的B02细胞和CHO细胞对矿化骨、骨唾液蛋白和胶原蛋白的侵袭和黏附显著增加。总体而言，我们的研究结果表明，肿瘤细胞中整合素α(v)β3的表达可能通过增加对骨的侵袭和黏附加速溶骨性病变的发展。
