Adhesion signature based enrichment of tumor initiating cells

Abstract

In spite of major therapeutic advances, cancer relapse and low rates of patient response to cancer therapeutics persist. This failure is due in part to a small subpopulation of tumor initiating cells (TICs) with stem cell-like properties that are responsible for the growth of the tumor and the progression of metastasis. These cells are capable of surviving chemotherapy, rendering them highly resistant to conventional cancer therapies. Although the question of whether TICs are stem cells remains a controversial topic in the cancer field, it has become increasingly evident that a better understanding of their biology and function is necessary to effectively treat cancer and eradicate tumors without allowing for relapse to occur. This project aimed to develop an objective, label-free, fast, and scalable method for cancer cell and TIC enrichment based on the adhesion strength signature of these cells. Currently, no efficient and reliable methods to isolate TICs exist. Although many in the field rely on surface marker expression profiles, these are variable and subjective, which hinders the study of TIC biology. Our lab has developed a technology to isolate cells based on their unique adhesion binding strength to a matrix. The novel technology (micro-Stem cell High- Efficiency Adhesion based Recovery [μSHEAR]) consists of a microfluidic device that applies varying degrees of detachment shear forces to adherent cells. Using this device, human pluripotent stem cells and their progeny have been isolated with high reproducibility, yield (>97%), purity (95-99%), and survival (>95%) rates (Singh et al, Nature Methods 2013). The process is fast (<10 min), label free, and scalable. Our hypothesis was that subtypes of cancer cells will exhibit distinct ‘adhesive force signatures’ that can be exploited to selectively purify TICs with high efficiency using the μSHEAR technology. The significance of this work was the development of a novel platform for objective, reliable, and scalable TIC purification.