INTEGRIN ALPHA(V)BETA(3) EXPRESSION BY BONE-RESIDING BREAST-CANCER METASTASES

Breast cancer metastasis to bone is a multistep process requiring atta chment of tumor cells to the bone and bone marrow environment. The pre cise adhesion molecules involved in skeletal homing of breast cancer t o bone are unknown but likely include integrins. We investigated the e xpression of vitronectin receptor (alpha(v) beta(3)) by breast cancer cells residing in bone because this heterodimer mediates osteoclast-bo ne recognition. We used immunohistochemistry and in situ hybridization in a systematic study of 22 bone biopsies containing breast cancer me tastases and available samples of corresponding primary tumors and nor mal breast and compared alpha(v) beta(3), alpha(2) beta(1), and alpha( v) beta(5) integrin expression. The results showed that alpha(v) beta( 3) was strongly expressed by normal breast epithelium and was decrease d in same and strongly expressed in other primary invasive breast carc inomas. In contrast, this integrin heterodimer was abundant in all bre ast cancer cells metastatic to bone. In situ hybridization revealed hi gh levels of steady-state mRNA corresponding to sites of protein expre ssion; alpha(2) beta(1) was weakly expressed in both primary and metas tatic tumors, and alpha(v) beta(5) was not detected. Our results showe d an overexpression of alpha(v) beta(3) by bone-residing breast cancer cells and suggest either subclonal selection of alpha(v) beta(3)-expr essing tumor cell populations or upregulation of alpha(v) beta(3) in t he bone microenvironment.