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.

Surfactant-free suspension polymerization of hydrophilic monomers with an oil-in-water system for the preparation of microparticles toward the selective isolation of tumor cells

“…[8][9][10] PMEA-coated substrates showed no cytotoxicity and an improved viability of tumor cells under serum-free conditions. 11 Furthermore, we demonstrated that polymer droplets composed of PMEA selectively accumulate in tumor cells, avoiding normal cells. [11][12][13] Thus, PMEA has the potential to selectively isolate tumor cells from blood samples regardless of their EpCAM expression.…”

“…11 Furthermore, we demonstrated that polymer droplets composed of PMEA selectively accumulate in tumor cells, avoiding normal cells. 11–13 Thus, PMEA has the potential to selectively isolate tumor cells from blood samples regardless of their EpCAM expression.…”

“…Our previous reports demonstrated that PMEA-coated substrates did not cause substantial cytotoxicity under serum-free conditions, but rather improved cell viability. 11 PMEA microparticles would not cause insignificant damage to captured tumor cells. On the other hand, the advantage of dynamic conditions using microparticles would be demonstrated in the presence of multiple cells, including tumor cells, platelets, and white and red blood cells.…”

Simple Detection and Culture of Circulating Tumor Cells from Colorectal Cancer Patients Using Poly(2-Methoxyethyl Acrylate)-Coated Plates

“…PMEA has been approved by the FDA for use in medical devices, and PMEA has the largest market share in the world as a nonthrombogenic coating agent for artificial oxygenators. Our team has demonstrated by in vitro studies that breast cancer and other tumor cells can attach to this blood-compatible PMEA via both integrin-dependent and -independent mechanisms [ 22 , 23 , 24 , 25 , 26 , 27 ], while platelets and other blood cells cannot attach to PMEA [ 28 , 29 , 30 , 31 , 32 , 33 ].…”

Nanoscopic analyses of cell-adhesive protein adsorption on poly(2-methoxyethyl acrylate) surfaces

“…14,15 Conversely, PMEA promoted cell adhesion and regulated cell functions such as proliferation and differentiation. [16][17][18] In addition, the droplets formed from PMEA selectively accumu-lated in tumor cells rather than in normal cells. 19 This is because the PMEA-coated surface enhanced the conformational changes in adsorbed fibronectin, an adhesive cell protein.…”