Tumor-Initiating Cells: Emerging Biophysical Methods of Isolation

Abstract

The discovery and subsequent isolation of tumor-initiating cells (TICs), a small population of highly tumorigenic and drug-resistant cancer cells also called cancer stem cells (CSCs), have revolutionized our understanding of cancer. TICs are isolated using various methodologies, including selection of surface marker expression, ALDH activity, suspension culture, and chemotherapy/drug resistance. These methods have several drawbacks, including their variability, lack of robustness and scalability, and low specificity. Alternative methods of purification take advantage of biophysical properties of TICs including their adhesion and stiffness. This review will provide a brief overview of TIC biology as well as review the most important methods of TIC isolation with a focus on biophysical methods of TIC purification.

Hydrodynamic shear-based purification of cancer cells with enhanced tumorigenic potential

“…Microfluidic cell isolation methods have emerged as powerful platforms for cell enrichment, particularly for cancer cells (as reviewed in [25,[62][63]). These systems employ differential surface marker expression [64][65] or differences in cell mechanical properties (e.g.…”

“…antibodies), are time consuming, require specialized equipment, and are difficult to scale-up. In contrast, label-free biophysical methods based on differential cell adhesion or stiffness have been explored to isolate cancer cells [25]. For example, increased cell elasticity is correlated to increased migratory behavior in cancer cells [26][27][28][29] and activation of the EMT program [30]; both of these biological phenomena correlate with TIC phenotype [31].…”

Research Progress of circRNAs in Glioblastoma

“…Nowadays, there are more and more researches on the mechanism of circRNAs generation. In addition to RBP can bind to circRNAs to reduce the regulation of RBP on target genes and affect tumorigenesis (Huang C.-K. et al, 2020;Li et al, 2020;Song et al, 2021), some RBP can also regulate the generation of circRNAs, which also has an important role in tumor development (2016;Liu Z. et al, 2021;Wang et al, 2021d;Wang and Lei, 2021;Yang T. et al, 2021). The translation function of circRNAs is also becoming a hot topic, and the translation initiation mechanism of circRNAs mainly includes cap-dependent, IRES-dependent, m6adependent and small ORF-dependent translation initiation (He L. et al, 2021;Wang X. et al, 2021), and circRNAs encode proteins with the function of suppressing tumor activity and protecting proteins from degradation (Chen C.-K. et al, 2021;Wang et al, 2021d;Ma et al, 2021;Qi et al, 2021).…”

“…The strong self-renewal ability, inherent high proliferative capacity and multidirectional differentiation together constitute the basic characteristics of malignant stem cells, among which the self-renewal ability is closely related to tumorigenesis and malignancy ( Ferragut et al, 2021 ; Mehraj et al, 2021 ; Yue et al, 2021 ). Over the past three to 4 decades, numerous studies have noted a potential link between stem cell systems and certain tumors, and a small proportion of tumor-initiating cells with stem cell properties, also known as tumor stem cells, have been identified in a variety of organs ( Cermeno and Garcia, 2016 ; Hass et al, 2020 ; Pan et al, 2021 ; Ryskalin et al, 2021 ). Tumor stem cells of glioma tissue origin have the capacity for self-renewal, homotransplantation into tumors, and differentiation into neurons and glial cells; it is now thought that they may be derived from genetically mutated neural stem cells, transiently expanded cells, neural progenitor cells, and even highly differentiated astrocytes and oligodendrocytes in normal brain tissue.…”