Abstract P4-04-02: Isolation and Characterization of Adult Mammary Stem Cells from the Periphery of Breast Cancer

Abstract

Abstract Background: Normal adult mammary stem cells (AMSCs) provide promising cell sources for breast reconstruction, especially after the resection of breast tumors. However, the potential targeting by carcinogenic events may convert normal AMSCs to cancer stem cells, posing a safety issue for applying the AMSCs for tissue regeneration in clinic. Objective: In the current study, we characterized a population of AMSCs isolated from the normal tissue at the periphery of human breast tumors and provided evidence that these AMSCs remain normal but not cancerous phenotypes and therefore, could be candidates for breast reconstruction. Methods: A population of AMSCs was isolated from the normal tissue surrounding primary breast tumors using immunomagnetic sorting. The stemness of these cells were examined by differentiation analysis and the gene expression profile compared to that of the cancer cells by microarray, with several differentially expressed candidate genes confirmed by both RT-PCR and Western blot assays. The in vivo tumorigenic capability of these cells were also investigated and compared to that of MCF-7 cell line. Results: The AMSCs were positive for stem cell markers, epithelial specific antigen (ESA) and keratin 19 (K19). When stimulated with the differentiation agent, basic fibroblast growth factor (bFGF), these AMSCs formed lobuloalveolar structure with myoepithelium that are positive for CALLA. The gene expression profiles revealed that compared to the cancer cells, see Table 1,2. AMSCs were low in oncogenes such as c-myc, Ras and c-erbB-2, but high in tumor suppressor genes including Rb1, Pten and CDKN2A, see table 1,2 and fig 1,2. When injected into nude mice, the AMSCs formed no tumors but regular mammary ductal structures. Conclusion: The AMSCs isolated from the normal tissue surrounding the primary breast cancers present features of normal mammary stem cells, therefore, are promising candidates for mammary reconstruction after breast tumor resection. Gene expression by western blot (sample 1, 2, 3 were breast cancer; sample 4,5 were mammary stem cells) CerbB2 rtranscription (sample 1, 2, 3 were breast cancer; sample 4,5 were mammary stem cells) Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-04-02.