There is an urgent need to identify targeting molecules to control invasion and metastasis in cancer patients. We first isolated cancer stem cells (CSCs) from SKOV3 ovarian cancer cells and then investigated the role of melatonin in invasiveness and migration of CSCs compared to SKOV3 cells. The proportion of CSCs in SKOV3 cells was as low as 1.28% with overexpression of both CD133 and CD44. The ability of spheroid formation along with SOX2 overexpression revealed a high self-renewal potential in isolated cells. Melatonin (3.4 mM) inhibited proliferation of CSCs by 23% which was confirmed by a marked decrease in protein expression of Ki67, as a proliferation marker. Applying luzindole, a melatonin receptor 1, 2 inhibitor, partially abolished anti-proliferative effect of melatonin. Melatonin also decreased Epithelial mesenchymal transition (EMT) related gene expressions including ZEB1, ZEB2, snail and vimentin with increase in E-cadherin as a negative EMT regulator. Incubation of CSCs with melatonin showed a marked decrease in matrix metalloproteinase 9 (MMP9) expression and activity. Melatonin also inhibited CSCs migration in a partially receptor dependent and PI3k and MAPK independent manner. Melatonin can be considered as an important adjuvant to control invasion and metastasis especially in patients with high melatonin receptor expression.

Cancer stem cells (CSCs) are tumor cells with initiating ability, self‐renewal potential, and intrinsic resistance to conventional therapeutics. Efficient isolation and characterization of CSCs pave the way for more comprehensive knowledge about tumorigenesis, heterogeneity, and chemoresistance. Also a better understanding of CSCs will lead to novel era of both basic and clinical cancer research, reclassification of human tumors, and development of innovative therapeutic strategies. Finding novel diagnostic and effective therapeutic strategies also enhance the success of treatment in cancer patients. There are various methods based on the characteristics of the CSCs to detect and isolate these cells, some of which have recently developed. This review summarized current techniques for effective isolation and characterization of CSCs with a focus on advantages and limitations of each method with clinical applications.

No abstract

No abstract