Breast cancer metastasis to bone is a multistep process requiring attachment of
tumor cells to the bone and bone marrow environment. The precise adhesion molecules involved in skeletal homing of
breast cancer to bone are unknown but likely include
integrins. We investigated the expression of
vitronectin receptor (alpha V beta 3) by
breast cancer cells residing in bone because this heterodimer mediates osteoclast-bone recognition. We used immunohistochemistry and in situ hybridization in a systematic study of 22 bone biopsies containing
breast cancer metastases and available samples of corresponding primary
tumors and normal breast and compared alpha V beta 3, alpha 2 beta 1, and alpha B
beta 5 integrin expression. The results showed that alpha V beta 3 was strongly expressed by normal breast epithelium and was decreased in some and strongly expressed in other primary invasive
breast carcinomas. In contrast, this
integrin heterodimer was abundant in all
breast cancer cells metastatic to bone. In situ hybridization revealed high levels of steady-state
mRNA corresponding to sites of
protein expression; alpha 2 beta 1 was weakly expressed in both primary and metastatic
tumors, and alpha V beta 5 was not detected. Our results showed an overexpression of alpha V beta 3 by bone-residing
breast cancer cells and suggest either subclonal selection of alpha V beta 3-expressing
tumor cell populations or upregulation of alpha V beta 3 in the bone microenvironment.