Health
Scientists Identify Unique Breast Cancer Cells That Control Their Ability to Proliferate and Colonize the Lungs
These cells can also trigger their own dormancy, allowing them to evade certain therapies
These cells can also trigger their own dormancy, allowing them to evade certain therapies
Newswise — New York, NY (September 20, 2022) — Scientists from The Tisch Cancer Institute have uncovered a mechanism by which certain breast cancer cells regulate their own metastases, fuel dissemination from the original tumor site, and determine routes to invade distant organs such as the lungs, according to a study published in Cell Reports in September.
For the first time, scientists have identified a type of cancer cell in triple negative breast tumors, which is highly efficient in invading and colonizing distant organs but slow their growth upon colonization. These cells have a hallmark of slowed production of a protein called srGAP1, which is usually attributed to cancer growth.
Scientists also found in animal models that these unique cells trigger a phenomenon that keeps them in a dormant state in distant organs such as the lungs. This is an important finding because cancer cells have to efficiently survive at distant sites, and staying in this “asleep” existence allows these cells to evade therapies that target cancer cells’ normal rapid growth. Cells that are missed could later become metastatic.
“Our findings emphasize the importance of considering phenotypic changes that could occur when treating cancer cells with therapeutic strategies that target proliferating cells such as chemotherapy,” said Jose Javier Bravo-Cordero, PhD, Associate Professor of Medicine (Hematology and Medical Oncology) at The Tisch Cancer Institute at Mount Sinai. “While these treatment regimens target dividing cells, they may also be selecting for more invasive tumor cells. Our studies suggest that more selective therapeutic strategies combining treatments against both dividing cells and invasive dormant cells may be necessary to prevent metastatic disease.”
To conduct this study, researchers used high-resolution in vivo imaging to visualize extravasation, the process of tumor cells exiting the blood vessels to enter a target tissue. This event was observed in real time, revealing with unprecedented detail the early stages of tumor extravasation. The microscopy studies revealed that after these tumor cells invade the lungs, they enter into a dormant state by secreting the protein TGFβ2. The studies also showed that interfering with that protein can block tumor cell invasion into the lungs.
Partners who contributed to this work include Stony Brook University, University of Illinois at Chicago, Janelia Research Campus at Howard Hughes Medical Institute and University of California at Berkeley.
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Mount Sinai Health System is one of the largest academic medical systems in the New York metro area, with more than 43,000 employees working across eight hospitals, over 400 outpatient practices, nearly 300 labs, a school of nursing, and a leading school of medicine and graduate education. Mount Sinai advances health for all people, everywhere, by taking on the most complex health care challenges of our time — discovering and applying new scientific learning and knowledge; developing safer, more effective treatments; educating the next generation of medical leaders and innovators; and supporting local communities by delivering high-quality care to all who need it.
Through the integration of its hospitals, labs, and schools, Mount Sinai offers comprehensive health care solutions from birth through geriatrics, leveraging innovative approaches such as artificial intelligence and informatics while keeping patients’ medical and emotional needs at the center of all treatment. The Health System includes approximately 7,300 primary and specialty care physicians; 13 joint-venture outpatient surgery centers throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and more than 30 affiliated community health centers. We are consistently ranked by U.S. News & World Report‘s Best Hospitals, receiving high “Honor Roll” status, and are highly ranked: No. 1 in Geriatrics and top 20 in Cardiology/Heart Surgery, Diabetes/Endocrinology, Gastroenterology/GI Surgery, Neurology/Neurosurgery, Orthopedics, Pulmonology/Lung Surgery, Rehabilitation, and Urology. New York Eye and Ear Infirmary of Mount Sinai is ranked No. 12 in Ophthalmology. U.S. News & World Report’s “Best Children’s Hospitals” ranks Mount Sinai Kravis Children’s Hospital among the country’s best in several pediatric specialties. The Icahn School of Medicine at Mount Sinai is one of three medical schools that have earned distinction by multiple indicators: It is consistently ranked in the top 20 by U.S. News & World Report‘s “Best Medical Schools,” aligned with a U.S. News & World Report “Honor Roll” Hospital, and top 20 in the nation for National Institutes of Health funding and top 5 in the nation for numerous basic and clinical research areas. Newsweek’s “The World’s Best Smart Hospitals” ranks The Mount Sinai Hospital as No. 1 in New York and in the top five globally, and Mount Sinai Morningside in the top 20 globally.
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