In vitro models of cancer stem cells and clinical applications

Abstract

Cancer cells, stem cells and cancer stem cells have for a long time played a significant role in the biomedical sciences. Though cancer therapy is more effective than it was a few years ago, the truth is that still none of the current non-surgical treatments can cure cancer effectively. The reason could be due to the subpopulation called “cancer stem cells” (CSCs), being defined as those cells within a tumour that have properties of stem cells: self-renewal and the ability for differentiation into multiple cell types that occur in tumours.The phenomenon of CSCs is based on their resistance to many of the current cancer therapies, which results in tumour relapse. Although further investigation regarding CSCs is still needed, there is already evidence that these cells may play an important role in the prognosis of cancer, progression and therapeutic strategy. Therefore, long-term patient survival may depend on the elimination of CSCs. Consequently, isolation of pure CSC populations or reprogramming of cancer cells into CSCs, from cancer cell lines or primary tumours, would be a useful tool to gain an in-depth knowledge about heterogeneity and plasticity of CSC phenotypes and therefore carcinogenesis. Herein, we will discuss current CSC models, methods used to characterize CSCs, candidate markers, characteristic signalling pathways and clinical applications of CSCs. Some examples of CSC-specific treatments that are currently in early clinical phases will also be presented in this review.

3D tumor spheroids as in vitro models to mimic in vivo human solid tumors resistance to therapeutic drugs

“…During the last years, the results obtained show the presence of a subpopulation of cancer cells with stem cell-like properties-CSC-in the mass of different tumors, such as breast, brain, colon, gastric, hepatic, lung, ovarian, pancreas, prostate, and skin cancers (Clevers, 2011;S. Franco et al, 2016).…”

Generation and characterization of hepatocellular carcinoma cell lines with enhanced cancer stem cell potential

“…These models will enable researchers to correlate certain CSC fractions to prognosis and to eventually develop novel HCSC biomarker sets as well as efficient CSC‐targeting treatment strategies. Mostly due to their ease of use and reasonable costs, cell culture based models represent the most frequent systems used to study CSCs and CSC associated features or mechanisms . In our study, we aimed to generate novel CSC enriched monoclonal cell lines of the well‐established HCC cell line HepG2.…”

“…In our study, we aimed to generate novel CSC enriched monoclonal cell lines of the well‐established HCC cell line HepG2. For this, we utilized the spheroid formation assay, which represents a commonly accepted method to enrich CSC populations . Our strategy gave rise to three distinct HepG2 sub‐cell lines, of which two HCSC enriched subclones were selected for detailed characterization.…”

Biliary tract cancer stem cells - translational options and challenges

“…The ability of CSCs to form tumors in immunodeficient mice at very low cell numbers surrogates their high tumorigenic potential[2]. Besides in vivo xenograft experiments, also several in vitro techniques are used in CSC research.…”

“…Since then, numerous of such tumor-initiating cells were identified in most solid tumors[2]. These tumor-initiating cells, also referred to as cancer stem cells (TICs or CSCs) have the ability to self-renew as well as to differentiate into different lineages - traits that they share with (adult) stem cells.…”