Breast cancer stem cells characterized by CD70 expression preferentially metastasize to the lungs.

Background: Cancer stem cells (CSCs) are believed to form metastases. We sought to determine whether CD70 + subpopulation in human breast cancers represents the CSCs accounting for distant metastasis.

Methods: We measured the expression levels of CD70 in breast cancer cell lines and 122 primary breast cancer samples. We characterized the functional roles of CD70 + subpopulation in distant metastasis of breast cancers.

Results: We observed a distinct pattern of CD70 expression in a panel of primary breast carcinoma samples, indicating that CD70 serves as a biomarker of lung-specific metastasis. CD70- and CD70+ cell populations isolated from breast cancer cell lines exhibited epithelial and mesenchymal phenotypes, respectively. CD70+ cells, but not CD70- cells, possessed self-renewal and differentiation potentials. Tumorsphere formation in suspension cultures and in vivo tumorigenicity were significantly greater in CD70+ cells than in CD70- cells. Furthermore, the development of lung metastases induced by orthotopic injection was markedly increased in mice inoculated with CD70 + cells. CD70 contributed to the promotion of lung metastases by enhancing self-renewal potential of CD70 + cells.

Conclusions: We isolated CSCs from primary human breast cancers and found that CD70 + subpopulations mediate lung-specific metastasis. These findings might be used to aid in selection of patients for postoperative adjuvant therapy.