Metastasis-Initiating Cells in Renal Cancer

Abstract

Metastasis is a complex process that propagates cells from the primary or initial site of the cancer occurrence to distant parts of the body. Cancer cells break from the cancer site and circulate through the bloodstream or lymph vessels, allowing them to reach nearly all parts of the body. These circulating tumour cells (CTCs) contain specialized metastasis-initiating cells (MICs) that reside in the biological heterogeneous primary tumour. Researchers have hypothesized that metastasis of renal cell carcinoma is initiated by circulation of MICs in patients’ blood and bone marrow. Based on the cancer stem/progenitor cell concept of carcinogenesis, understanding the molecular phenotypes of metastasis-initiating cells (MICs) in renal cancer could play a vital role in developing strategies for therapeutic interventions in renal cancer. Existence of MICs among CTCs in renal carcinoma has not been proven in large scale. However, some studies have reported that specialized markers are found on the surface of circulating cells from the primary tumour. In mice, MICs have been isolated from CTCs using such markers, which have then been transplanted into xenograft model to show whether they give rise to metastasis in different organs. Considering these findings, in this review we have attempted to summarize the studies connected with MICs and their gene expression profiles that are responsible for metastasis in renal cancer.

Comparative Gene Expression Profiling of Primary and Metastatic Renal Cell Carcinoma Stem Cell-Like Cancer Cells

“…This remains in accordance with recent progress in cancer research that has shown tumors as heterogeneous with multiple cell populations and developed as an offspring of SCLCCs [10–12]. Populations of SCLCCs also display a significant phenotypic plasticity and may arise in the process of and/or undergo EMT, which in turn favors metastatic spread and a drug-resistant phenotype [13–16]. …”

“…CD105 promotes angiogenesis, regulates cytoskeleton organization, and affects cell morphology and migration [27–29]. CD105+ cells may also promote tumor metastasis by circulating tumor cells [16, 30]. Bussolati et al isolated CD105+ cells and described them as tumor initiating in mice models based on cell isolation in patients undergoing radical nephrectomy [31].…”

Gene set enrichment analysis and ingenuity pathway analysis of metastatic clear cell renal cell carcinoma cell line

“…Approximately 30% of patients with RCC have advanced disease at their initial diagnosis, and 60% of these patients have greater mortality because of metastases and the aggressiveness of their disease (41,45,53). Metastasis of RCC has been reported to almost all organs in the human body, including the brain, skin, bones, pancreas, thyroid, lungs, and liver (4,6).…”

Overcoming tumor heterogeneity in the molecular diagnosis of urological cancers

“…Of note, the very nature of how the CTC is likely released would allow a potentially broader assessment of the tumor than by needle biopsy; however, whether these processes are passive or active and truly represent the complete tumor physiology has yet to be fully determined. CTCs have been identified in both RCC and bladder cancer but with considerable variability reported in the biology, origin and malignant significance of these cells, particularly with RCC [39]. Interestingly, CTCs in bladder cancer, however, appear to hold some promise in predicting early systemic disease, and the identification of survivin-expressing CTCs may even prove to be an independent prognostic factor for disease-free survival [37].…”