Researchers at the University of Massachusetts Amherst have received a five-year, $1.76 million grant from the National Cancer Institute to study how, in some people, cancer cells in the human body that have left the original site of the cancer change from dormant to active due to chemotherapy. They are developing implantable tissue-engineered microenvironments where it is possible to see in detail what causes that change in a living system.
The research team is headed by Jungwoo Lee, assistant professor of chemical engineering. It includes Ryan A. Carpenter, a graduate student. Lee says the team wants to see how dormant cancer cells in the bodies of some people can become activated when subject to chemotherapy – a frequent treatment used to kill metastasizing cancer cells in tumors. To do this, they have developed tissue-engineered microenvironments using a sponge-like hydrogel scaffold that can be implanted under the skin of mice. The implanted scaffolds encourage blood vessel formation and attract circulating tumor cells that have left the site of a primary breast tumor. Many of these tumor cells do not continue their growth immediately but lay dormant throughout the body in a similar manner in cancer patients.
“The tissue-engineered implantable metastasis model represents a unique opportunity to capture the critical events during dormant-to-active transition of disseminated tumor cells,” the team says.
Lee says chemotherapy eliminates actively growing disseminated tumor cells but associated tissue inflammation and remodeling possibly awake other dormant tumor cells, which could compromise the effectiveness of chemotherapy. One possible process is cluster formation of activated tumor cells. Such clusters of active cancer cells may help each other to survive even when the body’s defense mechanisms try to expel them. However, it has been difficult to capture early stage critical cellular events and long-term consequence in metastasis due to the lack of relevant experimental models.
To see long-term effects, the niches, as they develop tumors, can be transplanted to different mice who previously were cancer-free and have similar but fully functional immune systems. The implantable premetastatic niches established in a semi-transparent and standardized structure of hydrogel scaffolds are compatible with several types of advanced imaging techniques, which provide unique opportunities to see the impact of chemotherapy-induced tissue inflammation in awakening dormant tumor cells.
“The proposed research is significant because it has the potential to facilitate the development of better therapeutic regimens that can eliminate active residual tumor cells without activating dormant disseminated tumor cells and this would significantly improve long-term metastasis prevention,” Lee and his colleagues say.