Cancer Stem Cells in Renal Cell Carcinoma: Origins and Biomarkers

The term cancer stem cell (CSC) refers to a cancer cell with the following features: clonogenic ability, the expression of stem cell markers, differentiation into cells of different lineages, growth in nonadhesive spheroids, and the in vivo ability to generate serially transplantable tumors that reflect the heterogeneity of primary cancers (tumorigenicity). According to this model, CSCs may arise from normal stem cells, progenitor cells, and/or differentiated cells because of striking genetic/epigenetic mutations or from the fusion of tissue-specific stem cells with circulating bone marrow stem cells (BMSCs). CSCs use signaling pathways similar to those controlling cell fate during early embryogenesis (Notch, Wnt, Hedgehog, bone morphogenetic proteins (BMPs), fibroblast growth factors, leukemia inhibitory factor, and transforming growth factor-& beta;). Recent studies identified a subpopulation of CD133+/CD24+ cells from ccRCC specimens that displayed self-renewal ability and clonogenic multipotency. The development of agents targeting CSC signaling-specific pathways and not only surface proteins may ultimately become of utmost importance for patients with RCC.

Automated summary

Cancer stem cells (CSCs) possess several characteristics, including clonogenic ability, expression of stem cell markers, differentiation into different cell types, growth in nonadhesive spheroids, and the ability to generate tumors that reflect the heterogeneity of primary cancers. CSCs can arise from normal stem cells, progenitor cells, or differentiated cells due to genetic/epigenetic mutations or fusion with bone marrow stem cells. CSCs utilize signaling pathways similar to those involved in early embryonic development. Targeting these pathways, along with surface proteins, is important for treating RCC patients.