Immobilization platform to induce quiescence in dormancy-capable cancer cells

Abstract

Cancer dormancy emerges when tumor cells cease to proliferate but remain alive in a quiescent state. Recent evidence suggests that cancer cells can stay dormant in a patient’s body for years before returning to a proliferative state, leading to cancer relapse. The lack of a system to efficiently identify and study dormant cancer cells is currently limiting further diagnostic and treatment developments to prevent cancer relapse. Herein, we present a novel encapsulation platform to identify and study dormancy-capable cancer cells in a quiescent state by inhibiting proliferation through physical confinement. The platform involves the encapsulation of cells within a stiff silica-PEG hydrogel produced by a sol–gel technique. Cells are immobilized in a nondegradable microenvironment where proliferation and movement are inhibited due to physical confinement of the gel. The platform was tested using non-cancerous cell lines HFF, HUVEC, Jurkat, MEF, and MCF-10A, and cancer cell lines LnCAP, MCF-7, MCF10DCIS.com , MDA-MB-468, and OVCAR-5. Viability and metabolic activity measurements showed that MCF-7, LnCAP, and MCF10DCIS.COM cells remained metabolically active for up to 3 weeks while non-cancerous lines and the rest of the cancer cell lines did not survive after a few days. Ki-67 immunofluorescent staining confirmed that surviving MCF-7 cells underwent cell cycle arrest as early as 48 hours after encapsulation. Furthermore, following extraction and recovery, these cells resumed proliferation, indicating that the induced cell cycle arrest was reversible. These results conclude that physically inhibiting proliferation via the silica-PEG hydrogel system can be used to identify cells that can enter a quiescent state, setting the groundwork for this platform to be explored as a cancer cell dormancy model.