Cancer Stem Cells in Renal Cell Carcinoma: Origins and Biomarkers

Abstract

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-β). 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.

The Role of MUC1 in Renal Cell Carcinoma

“…To support the NEPC cancer stem cell (CSC) state, MUC1-C additionally activates the NOTCH1 stemness TF. It has been suggested that one of the variables influencing intra-tumor heterogeneity is CSCs [ 91 ]. On the other hand, new research has demonstrated that a tumor cell’s ability to look like a stem cell is flexible.…”

“…Many studies have suggested that stem cell-like CTCs could have a role in promoting the evolution and progression of different tumors [ 91 ]. The identification and characterization of cancer stem cells (CSCs) in renal cell carcinoma is still under investigation [ 138 , 139 ].…”

Identification of a lactate metabolism-related lncRNAs signature for predicting the prognosis in patients with kidney renal clear cell carcinoma

“…Moreover, accumulating evidence suggests that a subpopulation of cells within tumors, known as cancer stem cells (CSCs), possesses unique characteristics that contribute to tumor recurrence, metastasis, and resistance to conventional treatments. Lactic acid may play a role in metabolic adaptations of CSCs, influencing their preference for glycolytic or oxidative phosphorylation pathways based on contextual factors like oxygen tension and glucose availability ( 36 ). These findings suggested that the LMR lncRNAs may contribute to the discovery of regulatory mechanisms of tumor immunity and tumor progression.…”

Disturbances in Nitric Oxide Cycle and Related Molecular Pathways in Clear Cell Renal Cell Carcinoma

“…Recent studies have identified a subpopulation of CD133+/CD24+ cells in ccRCC specimens that exhibited self-renewal capacity and clonogenic multipotency. These cells are referred to as "cancer stem cells" (CSC), utilizing signalling pathways similar to those that control cell fate during early embryogenesis [95,96]. As discussed in this article, the NO/NOS system is interconnected with various tumour-promoting processes in the tumour microenvironment.…”