Prosective Cloning Of Highly Invasive Differentiated Breast Cancer Cells

Breast cancer consists of a variety of cell types with distinct phenotypes. Here, we examine the heterogeneity by a panel of normal human breast lineage markers from a recently described hierarchy. By use of multicolor imaging, we show that random heterogeneity is in fact patterned. Tumor cells exhibit traits of normal luminal-, and basal- progenitors, respectively. By combining fluorescence activated cell sorting and single cell cloning, we demonstrate that the patterned heterogeneity reflects a lineage hierarchy reminiscent of that seen in the normal breast. Distinct classes of tumor cells have differing functional abilities and behavior. Thus, multipotent basal-like tumor cells with stem cell properties give rise to lineage restricted tumor cells with luminal-like properties. Luminal-like tumor cells, in turn, are most aggressive as revealed by soft agar colony formation, invasiveness, and in vivo tumorigenecity. We therefore conclude that breast cancer heterogeneity, to some extend, arise as a consequence of normal-like lineage evolution. However, more importantly, the progeny of cancer stem cells remains deregulated raising serious doubts about the current concept of the cancer stem cell as the ultimate drug target. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 4277.