Newswise – An unhealthy gut causes changes in normal breast tissue that help breast cancer spread to other parts of the body, according to new research from the UVA Cancer Center.
The gut microbiome – the group of microbes that normally live inside us – can be disrupted by poor diet, long-term antibiotic use, obesity or other factors. When this happens, a patient’s microbiome reprograms important immune cells in healthy breast tissue, called mast cells, to facilitate the spread of cancer, according to the new discovery by UVA Health.
This discovery could help scientists develop ways to prevent breast cancer from spreading (spreading to other parts of the body). When it does, it is often fatal: only 29% of women with metastatic breast cancer survive five years; For men with metastatic breast cancer, this percentage is only 22%.
UV scientists say the finding could also allow doctors to predict which patients are most at risk of cancer recurrence after treatment.
“We have shown commensal gut dysbacteriosis, an unhealthy and inflammatory gut microbiome, systemically alters mammary tissues of non-cancer mice. Tissue changes promote mast cell infiltration that , in the presence of a tumor, facilitates breast metastasis.” “Mast cells that are recruited into the tissue environment during dysbiosis restructure the tissue structure in such a way that cancer cells metastasize to other organs.”
The microbiome and breast cancer
Rutkowski was a pioneer in revealing the surprising link between gut health and breast cancer. Her recent work reveals complex interactions between the gut microbiome and mast cells in the breast. Mast cells are blood cells that help regulate the body’s immune response to diseases and allergens. Rotkowski’s new work suggests that the gut microbiome can systemically influence the behavior and function of mast cells in the presence of tumors.
Rutkowski and her team found that an unhealthy microbiome caused a buildup of mast cells in the breast. These changes persisted after tumor formation in a mouse model of hormone receptor-positive breast cancer, making breast tissue a major stepping stone for cancer incursions into other parts of the body.
Moreover, the scientists found that mast cells increase the amount of collagen in the breast tissue of mice and stimulate early cancer spread. The process that led to the accumulation of mast cells prevented both, which greatly reduced the spread of the tumor to the lungs.
Based on lab results, the researchers examined tissue samples taken from human patients with hormone receptor-positive breast cancer. They found that these patients, like mice, had increased numbers of mast cells and increased deposits of collagen. The number of mast cells correlates with the amount of collagen, particularly the risk of recurrence of breast cancer in patients.
“Mast cells have had a controversial role in breast cancer, with some studies identifying a positive association with the outcome while others have identified negative associations,” said Rutkowski, from UVA University’s Department of Microbiology, Immunology and Cancer Biology. “Our investigation suggests that to better define the relationship between mast cells and the risk of breast metastasis, we should consider the functional features of mast cells, tissue collagen density and the location of mast cells in relation to the tumor.”
Eventually, she says, doctors may be able to target the gut mast cell relationship in breast cancer patients to help prevent cancer recurrence and spread. They may also be able to use the discovery to identify patients at risk of recurrence, allowing them to adapt a treatment strategy to prevent metastatic disease.
“Personalized medicine in oncology is a promising approach to facilitate better patient outcomes,” said researcher Tzu-Yu Feng, PhD, first author of a new scientific paper outlining the findings. “Our research on the intestinal mast cell axis has identified potential intervention points that can be targeted for a customized approach to treatment. The ultimate goal is to improve survival for patients diagnosed with breast cancer.”
Rutkowski’s cutting-edge research is part of the UVA Cancer Center’s urgent mission to better understand and treat cancer. UVA is one of only 52 cancer centers in the country classified as a comprehensive cancer center by the National Cancer Institute (NCI). This designation recognizes elite cancer centers with the nation’s most distinguished cancer research and treatment programs.
UVA Cancer Center is the only comprehensive cancer center in Virginia.
Rutkowski and her collaborators published their findings in the scientific journal Cancer Immunology Research. The research team consisted of Tzu-Yu Feng, Francesca N. Azar, Sally A. Dreger, Claire Buchta Rosean, Mitchell T. McGinty, Audrey M. Butelo, Sree H. Kolli, Maureen A. Fowler, Stephen D. Robinson and Melanie Rutkowski.
The work was supported by Susan J. Komen, Grant CCR17483602; National Cancer Institute of the National Institutes of Health, grant R01CA253285; and American Cancer Society, grants IRG 81-001-26. Additional support came from the UVA Cancer Centre, the BBSRC Strategic Programme, Gut Microbiome and Health, and Cancer Research UK.
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