Modulation of Biological Responses of Tumor Cells Adhered to Poly(2-methoxyethyl acrylate) with Increasing Cell Viability under Serum-Free Conditions.

Abstract

Circulating tumor cells in body fluids are important biomarkers in cancer diagnosis. The culture of tumor cells isolated from body fluids can provide intrinsic information about tumors and can be used to screen for the best anticancer drugs. However, the culture of primary tumor cells has been hindered by their low viability and difficulties in recapitulating the phenotype of primary tumors in in vitro culture. The culture of tumor cells under serum-free conditions is one of the methodologies to maintain the phenotype and genotype of primary tumors. Poly(2-methoxyethyl acrylate) (PMEA)-coated substrates have been investigated to prolong the proliferation of tumor cells under serum-free conditions. In this study, we investigated the detailed behavior and the mechanism of the increase in tumor cell viability after adherence to PMEA substrates. The blebbing formation of tumor cells on PMEA was attributed not to apoptosis but to the low adhesion strength of cells on PMEA. Moreover, blebbing tumor cells showed amoeboid movement and formed clusters with other cells via N-cadherin, leading to an increase in tumor cell viability. Furthermore, the behaviors of tumor cells adhered to PMEA under serum-free conditions were involved in the activation of the PI3K and Rho-associated protein kinase pathways. Thus, we propose that PMEA would be suitable for the development of devices to cultivate primary tumor cells under serum-free conditions for the label-free diagnosis of cancer.