Abstract 3314: Side population in renal cell carcinoma cell line is enriched with drug resistant, but not tumor initiating cells

Abstract

Abstract Several lines of evidences suggested the presence of tumor initiating cells in renal cell carcinoma (RCC) and side population (SP) may be enriched with these “cancer stem cells (CSC)”. Herein we demonstrated the presence of Side population in 10 RCC cell lines ranging from 0.19 - 36.1%. Lineage tracing experiments showed that the SP can be enriched through sequential sorting and can differentiate into non-SP (NSP) which constitutes the bulk of the cells. The NSP can also formed back the original population of the SP in CRL1611 cells. Interestingly, the presence of NSP seem to prevent the SP from differentiating into NSP. The SP cells have about 15% higher proliferation rate and 50% greater colony forming efficiency which are reported characteristics of CSC. SP expresses higher level of cMyc, but lower level of CD105 as compared to the NSP. On the contrary, there is no difference in tumorigenic potential between SP and NSP using both correlation and in vivo studies. However, we verified that SP are 10% more resistance to mTOR inhibitor, RAD001 which coincide with higher expression of drug resistance membrane transporters ABCB1 and ABCG2 in SP cells. Treatment with RAD001 increases the amount of SP concomitantly up regulate ABCB1 and ABCC1 significantly. Taken together, Hoechst dye exclusion did not define tumor initiating cells, but is a valuable technique for identifying drug resistance cells in RCC. 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 3314.