Integrin binding uniquely regulates tropic breast cancer cell phenotypes in vitro

Breast cancer preferentially spreads to the bone, brain, liver, and lung, and this tissue-specific spread (tropism) is not well understood. The diversity of tissue sites often recipient of metastatic colonization suggests a role for the extracellular matrix (ECM) in tropism. We created a biomaterial platform that varies ECM type and composition, inspired by the bone, brain, and lung tissues, in order to study integrin-mediated adhesion and motility phenotypes. We report that bone, brain, and lung tropic breast cancer cells respond to ECM variations uniquely, implicating integrin binding in tropism. We confirmed these phenotypes in other metastatic cell lines, establishing a connection between in vitro phenotype and in vivo fate. We report that integrin-targeting alters the tropic phenotype, and provide insight toward integrins as druggable targets for metastatic disease. In sum, we emphasize the importance of the ECM and engineered microenvironments in order to understand breast cancer spread.