Recent findings from Lawrence Berkeley National Laboratory reveal one of the causes of some breast cancer patients’ relapses years after treatment.
In a study published Sunday in Nature Cell Biology, Berkeley lab researchers Mina Bissell, Cyrus Ghajar and other co-authors explain how tumor cells can spread from the breast tissue to other organs, such as the lungs, brain or liver, where they remain dormant and undetected until they eventually metastasize.
“In a lot of patients, what happens is that these metastases don’t emerge right away,” Ghajar said. “They’ll be disease-free for many years — in some cases, decades. These cells are just sitting in other organs and are potentially ticking time bombs.”
One out of every five women affected with breast cancer will relapse somewhere between the seventh and 25th year after treatment, Ghajar said.
The study revealed that disseminated breast tumor cells can reside on the surrounding microvasculature and maintain a dormant state for a long period of time as long as the microvasculature remains stable.
The researchers conducted the study by engineering the “microvascular niche” of metastatic sites, such as the lung, with human cells from these organs. Using these models, they were able to show that endothelial cells, which line the inner surface of blood vessels, induce and maintain the quiescent state of tumor cells by secreting a protein found in a specialized sleeve of matrix lining the outside of blood vessels.
This state, however, is not regulated by all patients, and metastasis can occur when the dormant state of the microvasculature is disrupted. Neovascular tips of niches can sprout, causing adjacent tumor cells to proliferate with normal tissue growth. When this happens, suppressive factors provided by the epithelium are lost and superseded by an array of promoting factors. In other contexts, these promoting factors have been shown to promote metastasis.
The exploration of the nature of microenvironments surrounding tumors is what makes this study so unique, according to Patricia Ganz, director of cancer prevention and control research at UCLA.
“If we don’t find strategies to treat the microenvironment, we won’t prevent recurrence,” Ganz said. “People have really focused on the tumor cells, but if we can change the microenvironment, we may be able to prevent tumors from growing.”
The findings of this study have no immediate effects for patients, but they offer valuable insight into possibilities for further research.
“It’s particularly important for women who after 15, 20 years find out they have relapsed,” said Dolores Moorehead, client services manager for the Women’s Cancer Resource Center. “It’s a positive step in making some progress.”
Ghajar says he is optimistic about future supplementary therapies that will help keep these “potentially ticking time bombs” ticking forever.
“We can envision a scenario whereby we’ve taken cancer from a disease that is unmanageable to a disease where we’re actually proactive about it,” Ghajar said.
Contact Angelica Villegas at [email protected]