How do cancer cells travel beyond the primary tumor, stay dormant for years and then suddenly wake up, causing cancer to recur? Researchers at Mount Sinai believe they may have found one answer—and that the discovery could offer new tools for predicting and preventing cancer relapses.
The researchers discovered cancer cells stay dormant by secreting a specific type of collagen protein into their environment. When collagen levels fall, the cells turn malignant. Adding collagen to the cancer cells’ environment forces them to remain in the dormant state, they reported in Nature Cancer.
The Mount Sinai team used high-resolution imaging to track dormant cancer cells in mouse models of breast cancer and head and neck cancer. The technology allowed them to observe changes in the cells and the extracellular matrix when dormant, distant tumor cells started to awaken. That’s how they discovered the dormant cells were secreting type 3 collagen and then waking up when levels of the protein started to wane.
The Mount Sinai team went on to boost levels of type 3 collagen in the mouse models, specifically in the environment surrounding cells that had left the primary tumors. That forced the cells to become dormant, they reported.
This is one of several novel strategies that have been proposed in recent years for preventing dormant cancer cells from becoming metastatic. In June, for example, a Georgetown University team identified “enabler” cancer cells that express the protein AIB1-Delta4, prompting metastasis of triple-negative breast cancer. They suggested drugs could be developed to target weaknesses in these enabler cells.
In October, University of California researchers published a map of protein-protein interactions that drive cancer metastasis—a resource they hope will lead to novel treatment strategies for a variety of cancers.
As part of their study, the Mount Sinai researchers showed that by measuring collagen in patient samples, they could predict cancer metastasis and recurrence. They suggested that their findings could inspire the development of drugs that specifically target dormant cancer cells.
“As the biology of tumor dormancy gets uncovered and new specific drugs are developed, a combination of dormancy-inducing treatments with therapies that specifically target dormant cells will ultimately prevent local recurrence and metastasis and pave the way to cancer remission,” said senior author Jose Javier Bravo-Cordero, Ph.D., associate professor of medicine at the Tisch Cancer Institute at Mount Sinai, in a statement.