Biomedicine

Tumor recurrence is a major clinical problem in ovarian cancers with five-year survival rates of less than 20%, with recurrences observed often within months of cytoreductive surgery. Recent evidence suggests that solitary cancer cells can be shed into the bloodstream even at early stages of tumor growth, and infiltrate into distant organs. As ideal conditions for colonization may not exist at the new site, most cancer cells die off, but a certain population of cells is known to transition into a reversibly growth-arrested (dormant) state and survive. These cells can then stay dormant for years to decades, awaken for unknown reasons and generate metastases, eventually killing the patient as these dormant cancer cells, which are non-proliferative, are impossible to kill because chemotherapeutic agents usually target rapidly proliferating cells.

We have recently shown that inhibition of proliferation imposes a specific stress, enabling selection for the dormancy-capable cells within a mixed population of cells. In our method, cells are suspended in a synthetic silica sol which rapidly gels and immobilizes the cells in a highly permeable yet very stiff silica matrix, inhibiting their proliferation. The gel is then incubated in media for 3-5 days, selecting for dormant cells. Furthermore, the silica gel we developed is mechanically reversible (shear-thinning), enabling release of the immobilized cells on demand. This is the first and only non-proliferative method used for dormancy-capable cell isolation (US patent no 9,427,408).

immobilization

The fluorescent images and the plot above show the survival difference between dormancy-prone (MCF-7) and dormancy-resistant (MDA-MB-468) breast cancer cell lines when they are immobilized in the synthetic silica gel we developed.

Some questions we seek answers to:

What makes a cell dormancy-capable?

What is the role of the microenvironment on inducing or terminating dormancy?

Can we use this method to predict chemoresistance?

Can we use this technique to determine molecular targets in dormant cells?