Integrin αvβ3 Expression by Bone-residing Breast Cancer Metastases

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Abstract
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]v[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 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]v[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. (C) Lippincott-Raven Publishers.