Abstract 2314: Epithelial-mesenchymal transition derived cells exhibit multi-lineage differentiation potential similar to mesenchymal stem cells

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC The epithelial-to-mesenchymal transition (EMT) is an embryonic process that becomes latent in most normal adult tissues. Recently, we have shown that induction of EMT endows stem cell traits to breast epithelial cells. Mesenchymal stem cells (MSC) have the capacity to self-renew and differentiate into multiple tissue lineages. We hypothesized that the activation of EMT by ectopic expression of Twist, Snail or TGF-β in immortalized human mammary epithelial cells (HMEC) will result in the generation of cells with a phenotype and functionality similar to MSC. We found that the EMT-derived cells not only showed similar morphology but also displayed the typical MSC phenotype i.e. CD44+, CD24− and CD45−. Alternatively, MSC expressed EMT inducing genes such as Twist, Snail and FOXC2. Interestingly, CD140b (PDGFR-β), a marker for naive MSC, was exclusively expressed in EMT-derived cells compared to their epithelial counterparts. Moreover, functional analysis revealed that EMT-derived but not the control cells differentiate into Alizarin Red S-positive mature osteoblasts, Oil Red O-positive adipocytes and Alcian Blue-positive chondrocytes similar to MSC. We also observed that EMT-derived but not control cells invade and migrate towards MDA-MB-231 tumor cells in-vitro similar to MSC, displaying the characteristic tropism of MSC for tumor cells as previously reported by us. In-vivo wound homing assays in nude mice revealed that the EMT-derived cells home to wound sites similar to MSC. In conclusion, we demonstrated that the EMT-derived cells are similar to MSC in gene-expression, multi-lineage differentiation, migration towards tumor cells and their ability to home to wounds. These results also suggest that EMT-derived MSC are active participants in cancer growth and invasion. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2314.