Researchers have identified a population of clear cell renal cell carcinoma (ccRCC) cells positive for the CTR2 marker that possess some stem-cell-like features and are able to induce an angiogenic response in vivo.
In addition, targeting renal cancer cells expressing CTR2 was shown to decrease resistance to cisplatin.
“The identification of these cancer cells in ccRCC and related markers could have a role in supporting the diagnosis and prognosis of patients with RCC and … improving … therapeutic strategies,” say Giuseppe Lucarelli and co-authors from the University of Bari in Italy.
Lucarelli and team set out to characterise a population of CD133- and CD24-positive RCC-derived cells (RDCs) by comparing them with a CD133- and CD24-positive population of normal tubular adult renal progenitor cells (tARPCs)
They collected samples of both healthy tissue and tumour specimens from 40 patients with ccRCC and then selected for those cells that were positive for CD133 and CD24.
CTR2 proteins were expressed on 98.2% of RDCs, whereas tARPCs did not express the marker at all or expressed it at very low levels. The researchers also note that, in situ, CD133 was expressed in both RDCs and tARPCs, but that CTR2 was only expressed in RDCs, making CD133/CTR2 co-expression a potential marker of RDCs.
Intriguingly, pre-treatment of three different clones of RDCs with a specific CTR2-blocking antibody resulted in significantly greater sensitivity to cisplatin compared with unblocked RDCs.
RDCs cells expressing CTR2 had stem-cell-like properties, with the capacity to differentiate into different kinds of cells, such as adipocytes or epithelial cells, depending on their surrounding medium. They were also able to induce angiogenesis in vivo.
The team used fluorescence-activated cell sorting analysis to show that neither RDCs nor tARPCs expressed mesenchymal stem cell markers, suggesting that they do not have a mesenchymal origin.
Further analysis of marker expression indicated that RDCs were less differentiated than tARPCs. RDCs were also able to form tumour colonies in vitro.
Lucarelli and colleagues performed whole genome-wide gene expression profiling to identify 72 genes that discriminated RDCs from tARPCs, with the cell-mediated immune response, chemotaxis and invasion of tumour cells, and cell-cycle-related processes being among the most affected biological pathways.
“Our results indicate the presence, in ccRCC, of a CD133+/CD24+/CTR2+ cancer cells population,” they write in the Journal of Urology. “These cells possess some stem cell-like features, including in vitro self-maintenance and differentiating capabilities, and are able to induce an angiogenic response in vivo.”
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