What happens during tumor remission? After chemotherapy, tumor cell numbers may be reduced, or surviving cells may enter an altered, dormant state. Evidence for dormancy now comes from Catherine Shachaf, Dean Felsher (Stanford University, Stanford, CA), and colleagues. In their mouse model, liver tumors can be forced into dormancy and then reawakened at will.
As in previous studies, regression was induced by shutting off the oversupply of MYC, in this case using a tetracycline-controlled promoter. Transgenic mice took ~12 weeks to develop the MYC-induced tumors, but within 4 days of MYC inactivation the cells died or differentiated into normal liver cells. Tumors regressed but could later be reactivated by switching MYC back on.
The persistence of dormant tumor cells was demonstrated by transplanting tumor cells containing transgenes for both luciferase and the tetracycline-controlled MYC. Even when MYC was inactivated the luciferase signal persisted in the transplanted cells, which looked like normal liver cells. Turning MYC back on restored tumorigenesis, increasing cell number and thus luciferase activity.
Reversible dormancy has not been seen in previous MYC inactivation studies. Felsher believes that the differences are explained by the properties of the tumors' originating tissues. Lacking MYC, tumor cells from a terminally differentiated tissue such as bone resort to terminal differentiation; those from the apoptotic-prone hematopoietic compartment die; and those from liver (a tissue that is rich in stem cells and can regenerate) differentiate but produce many stem cells. It is those stem cells that may perpetuate the dormant state and that Felsher wants to understand.