Abstract 2377: Bone-derived osteopontin mediates the migration and stem-like properties of breast cancer cells

Abstract

Abstract Metastatic breast cancer has an affinity for certain organs and tissues, a phenomenon termed organ tropism. Of particular interest is breast cancer's preference for bone, since this is the most common site of metastasis in breast cancer patients. In addition, research suggests that breast cancer cells that do metastasize may have stem-like properties, including the ability to self-renew and differentiate into a heterogeneous tumor. These cells can be identified by their high aldehyde dehydrogenase activity (ALDH) and/or CD44+CD24- phenotype. However, it is unclear whether properties of the organ microenvironment or the stem-like cancer cells (or both) facilitate metastatic organ tropism. In the current study, we tested the hypothesis that bone marrow-conditioned media (an ex vivo representation of the bone microenvironment) contains specific soluble factors that enhance the growth and migration of whole population and ALDHhiCD44+CD24- breast cancer cells. Bone marrow-conditioned media (BMCM) generated from the bones of athymic nude mice was analyzed for the presence and identity of soluble factors using protein arrays. Osteopontin (OPN) was detected in the BMCM in significant amounts by the protein array and confirmed by ELISA. OPN was then depleted from the BMCM using immunoprecipitation and migration of MDA-MB-231 and SUM-159 breast cancer cells to the BMCM was assessed. Results indicate that bone-derived OPN significantly enhances MDA-MB-231 and SUM-159 breast cancer cell migration (P<0.05). Additionally, bone-derived OPN enhances the migration of ALDHhiCD44+CD24- MDA-MB-231 breast cancer stem cells relative to their ALDHlowCD44-CD24+ counterparts (P<0.05). The effect of bone-derived OPN on the tumorsphere forming abilities of whole population and ALDHhiCD44+CD24- MDA-MB-231 was also assessed; bone-derived OPN significantly enhances the tumorsphere forming abilities of whole population and stem-like MDA-MB-231 breast cancer cells (P<0.05). The interaction between bone-derived OPN and its cell surface receptors CD44 and αvβ5 in breast cancer cell migration to BMCM was also investigated using blocking antibodies. We observed that both whole population MDA-MB-231 and SUM-159 breast cancer cells interact with bone-derived OPN via CD44 and αvβ5 (P<0.05). Ongoing studies are investigating the activation of OPN-mediated signaling pathways in breast cancer cells as well as the role of CD44 and other cell surface integrins in the tumorsphere forming abilities of breast cancer cells. Overall, elucidation of the interactions between bone-derived OPN and breast cancer cells could contribute to future development of novel therapeutics that interrupt these interactions in the bone marrow niche, thereby improving breast cancer patient prognosis. Citation Format: Graciella M. Pio. Bone-derived osteopontin mediates the migration and stem-like properties of breast cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2377. doi:10.1158/1538-7445.AM2015-2377