Abstract
Epithelioid and fibroblastoid subsets coexist in the human sarcomatoid renal cell carcinoma (sRCC) cell line, RCC52, according to previous clonal studies. Herein, using monoclonal antibodies to CD44 and CD24 markers, we identified and isolated these two populations, and showed that CD44bright/CD24dim and CD44bright/CD24bright phenotypes correspond to epithelioid and fibroblastoid subsets, respectively. Both sorted subsets displayed different levels of tumorigenicity in xenotransplantation, indicating that each harbored its own cancer stem cells (CSCs). The CD44bright/CD24bright subset, associated with higher expression of MMP-7, -8 and TIMP-1 transcripts, showed greater migratory/invasive potential than the CD44bright/CD24dim subset, which was associated with higher expression of MMP-2, -9 and TIMP-2 transcripts. Both subsets differentially expressed stemness gene products c-Myc, Oct4A, Notch1, Notch2 and Notch3, and the RCC stem cell marker, CD105 in 4-5% of RCC52 cells. These results suggest the presence of CSCs in both sRCC subsets for the first time and should therefore be considered potential therapeutic targets for this aggressive malignancy.
Highlights
Renal cell carcinoma (RCC) accounts for approximately 3% of human malignancies, has a high metastatic index at diagnosis and a high rate of relapse [1, 2]
The extent of tumorigenicity induced by the epthelioid sublines was far less than that by the parental RCC52 cells
We may have only selected and used a limited number of clonal sublines in that study [29]. These clonal sublines might not represent the whole spectrum of each given subset population of RCC52
Summary
Renal cell carcinoma (RCC) accounts for approximately 3% of human malignancies, has a high metastatic index at diagnosis and a high rate of relapse [1, 2]. We found that the CD44bright/CD24bright sorted subset invariably resulted in much larger xenografts as a function of time, when compared with those developed by either the parental cells or the CD44bright/CD24dim sorted subset These results indicate that both sorted cell subsets of the RCC52 cell line/tumor harbored different classes of CSCs. The results obtained with sorted cells are likely to represent the true picture of this cell line/tumor in in vivo situations, since the spectra of whole cell populations of each sorted subset were all being considered and analyzed. The results obtained with sorted cells are likely to represent the true picture of this cell line/tumor in in vivo situations, since the spectra of whole cell populations of each sorted subset were all being considered and analyzed This is in contrast to our previous findings in which only small numbers of clonal isolates were investigated; these clonal sublines from the two morphologically distinct subsets were likely under representation of RCC52 cells [29]
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