Differential Expression Of Cd44 And Cd24 Markers Discriminates The Epithelioid From Fibroblastoid Subset In A Sarcomatoid Renal Cell Carcinoma Cell Line: Evidence Of The Existence Of Cancer Stem Cells In Both Subsets

The co-existence of epithelioid and fibroblastoid subsets in the human sarcomatoid renal carcinoma cell line, RCC52, has been demonstrated previously based on clonal studies, in which only the epithelioid subset was found to be tumorigenic in NOD/SCID mice. Since only few clonal isolates were used to analyze in that study, we argued that the tumorigenicity results might not be truly reflective of this tumor line. We therefore in this study determined to use cytofluorometrically sorted cells to re-evaluate certain biological parameters including xenotransplantation. Using two monoclonal antibodies to CD44 and CD24 markers, we succeeded in identification and isolation of the two populations, and showed the CD44bright/CD24dim and CD44bright/CD24bright phenotypes corresponding to the epithelioid and fibroblastoid subsets, respectively. At variance with the results of clonal studies, both cytofluorometrically sorted subsets displayed different but significant degrees of tumorigenicities, indicating that each subset harbored its own cancer stem cells (CSCs). In consistence with the tumorigenicity findings, both sorted subsets showed in vitro migratory/invasive potential with greater ability exhibited by the CD44bright/CD24bright subset which was associated with higher expression of MMP-7, -8 and TIMP-1 transcripts. On the other hand, the CD44bright/CD24dim subset was found to be associated with higher expression of MMP-2, -9 and TIMP-2 transcripts. Furthermore, both sorted subsets expressed the RCC stem cell marker CD105 in a small proportion of cells (4-5%), and were able to covert to PAX2+ clear cells in areas in the xenografts to a greater extent by the CD44bright/CD24dim subset, highlighting high plasticity of each subset in different ways. Collectively, our findings confirm the co-existence of two morphologically and phenotypically distinct subsets, and document the presence of CSCs in both subsets for the first time in sarcomatoid RCC. The CSCs/mCSCs in the two subsets should therefore be considered as emerging therapeutic targets in the design of future treatment strategies for this subtype of renal cancer. Citation Format: Chin-Hsuan Hsieh, Cheng-Keng Chuang, See-Tung Pang, Samuel Chien, Paul Lin, Shuen-Kuei Liao. Differential expression of CD44 and CD24 markers discriminates the epithelioid from fibroblastoid subset in a sarcomatoid renal cell carcinoma cell line: evidence of the existence of cancer stem cells in both subsets. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3349.