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
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 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.
About the Mount Sinai Health System
Mount Sinai Health System is one of the nation’s leading integrated academic health systems and one of the largest in the New York metropolitan area. Its comprehensive system includes seven hospitals, more than 400 outpatient practices, over 600 research and clinical laboratories, the Icahn School of Medicine at Mount Sinai, the Graduate School of Biomedical Sciences, and the Mount Sinai Phillips School of Nursing. Together, the Health System comprises approximately 48,000 employees, more than 9,000 physicians, and 8,600 nurses.
As a leading learning health system, Mount Sinai combines clinical expertise with scientific discovery to improve patient care while training the next generation of health care and biomedical leaders. The Health System provides care across every stage of life, from prenatal care through geriatrics, while advancing personalized medicine through artificial intelligence, data science, and biomedical research.
Mount Sinai is consistently recognized among the nation’s leading academic health systems for patient care, research, and education. The Mount Sinai Hospital is ranked No. 1 in New York by Newsweek and No. 5 on the magazine’s World’s Best Hospitals list. The Icahn School of Medicine at Mount Sinai ranks No. 11 among U.S. medical schools and No. 1 among freestanding medical schools for National Institutes of Health funding, reflecting the strength of its scientific enterprise and leadership in biomedical research.