RESUMEN
Tumor-initiating cells (TICs), a subpopulation of cancerous cells with high tumorigenic potential and stem-cell-like properties, drive tumor progression and are resistant to conventional therapies. Identification and isolation of TICs are limited by their low frequency and lack of robust markers. Here, we characterize the heterogeneous adhesive properties of a panel of human and murine cancer cells and demonstrate differences in adhesion strength among cells, which exhibit TIC properties and those that do not. These differences in adhesion strength were exploited to rapidly (~10 min) and efficiently isolate cancerous cells with increased tumorigenic potential in a label-free manner by use of a microfluidic technology. Isolated murine and human cancer cells gave rise to larger tumors with increased growth rate and higher frequency in both immunocompetent and immunocompromised mice, respectively. This rapid and label-free TIC isolation technology has the potential to be a valuable tool for facilitating research into TIC biology and the development of more efficient diagnostics and cancer therapies.
Asunto(s)
Carcinogénesis/patología , Adhesión Celular , Separación Celular/métodos , Hidrodinámica , Neoplasias/fisiopatología , Células Madre Neoplásicas/patología , Animales , Neoplasias de la Mama/patología , Línea Celular Tumoral , Progresión de la Enfermedad , Femenino , Proteínas Fluorescentes Verdes/metabolismo , Humanos , Células MCF-7 , Ratones , Ratones Endogámicos C57BL , Ratones SCID , Microfluídica , Transducción de Señal , Estrés MecánicoRESUMEN
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.