Abstract BSF1-1: Single Cell Analysis of Normal and Tumor Breast Epithelium Reveals Differential Use of Signalling Pathways by Novel Populations

Abstract

Abstract Primary human tissue contains a complex mixture of cell types which can only be partially purified by cell sorting based on surface markers. To gain further insight into mammary gland and tumor biology, we performed highly parallel single cell multiplexed gene expression measurements on individual normal and malignant mammary cells. This approach enabled discovery of novel normal mammary stem cell markers and gave insights into normal and malignant tissue architecture. We identified two distinct normal mammary stem cell populations: a proliferating, stem cell population that expresses basal cell markers and shows evidence of activation of the Wnt/β-catenin signaling pathway components and a second, Axin2-, CD44-/low quiescent normal stem cell population which does not express basal cell markers. Both populations had similar engraftment ability in vivo, demonstrating that there are likely two physiological stem cell states. Single cell analysis of estrogen receptor positive (ER+) breast tumors revealed similar cellular populations in cancer cells that resemble the normal mammary duct architecture. Remarkably, the expression of therapeutic targets such as growth factor receptors and the estrogen receptor differed between the different cell compartments. Most notably, the Axin2- cell population did not express ER or TOPO2, the target of Adriamycin, one of the most effective drugs for the treatment of breast cancer, suggesting that this population is not directly targeted by many therapeutic agents routinely used for the treatment of ER+ breast cancer. Our results show that single cell analyses might be useful for developing new strategies for treating cancer by identifying the expression of therapeutic targets by each of the cancer cell populations that make up a particular tumor. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr BSF1-1.