Cleveland: A previously unknown variant of an extensively studied protein has been found to inhibit the growth of tumors and slow the development of new blood vessels necessary for cancers to metastasize, according to Cleveland Clinic research published today in Cell.
The creation of new blood vessels, or angiogenesis, is a vital part of cancer growth and metastasis. Blood vessels carry nutrients and oxygen, which tumors need to survive, expand, and migrate to other parts of the body. A family of proteins called vascular endothelial growth factors (VEGFs) are behind the process of angiogenesis, and one particular protein, VEGF-A, is the principal driver in the process.
However, a research team led by Paul Fox, Ph.D., of the Department of Cellular and Molecular Medicine in Cleveland Clinic's Lerner Research Institute, has discovered that a variant of VEGF-A, one they call VEGF-Ax, actually decreases angiogenesis, cutting off the blood supply to tumors and inhibiting their development in animal models.
"This research is significant because it will open new avenues of angiogenesis and cancer research. It is important for patients as it could potentially lead to new diagnostic tools and improved treatments to reduce the spread of cancer." Dr. Fox said. "It is truly remarkable that a small change in a protein sequence leads not just to a protein with a different function, but one with a function completely opposite to the original. In the context of cancer, the small extension changes a very 'bad' protein into a very 'good' one."
VEGF-Ax is 22 amino acids longer that VEGF-A, and is formed when the ribosome—the cellular machinery that translates genes (actually messenger RNAs) into proteins—reads through its genetic stop sign in a process called programmed translational readthrough.
This research was supported by grants from the National Institutes of Health (P01 HL029582, P01 HL076491, R01 GM086430, and R21 HL094841).
About Cleveland Clinic
Cleveland Clinic is a nonprofit multispecialty academic medical center that integrates clinical and hospital care with research and education. Located in Cleveland, Ohio, it was founded in 1921 by four renowned physicians with a vision of providing outstanding patient care based upon the principles of cooperation, compassion and innovation. Cleveland Clinic has pioneered many medical breakthroughs, including coronary artery bypass surgery and the first face transplant in the United States. U.S. News & World Report consistently names Cleveland Clinic as one of the nation's best hospitals in its annual "America's Best Hospitals" survey. More than 3,000 full-time salaried physicians and researchers and 11,000 nurses represent 120 medical specialties and subspecialties. The Cleveland Clinic health system includes a main campus near downtown Cleveland, eight community hospitals, more than 75 Northern Ohio outpatient locations, including 16 full-service Family Health Centers, Cleveland Clinic Florida, the Lou Ruvo Center for Brain Health in Las Vegas, Cleveland Clinic Canada, and, scheduled to begin seeing patients in 2015, Cleveland Clinic Abu Dhabi. In 2012, there were 5.1 million outpatient visits throughout the Cleveland Clinic health system and 157,000 hospital admissions. Patients came for treatment from every state and from more than 130 countries. Visit us at http://www.clevelandclinic.org. Follow us at http://www.twitter.com/ClevelandClinic.
About the Lerner Research Institute
The Lerner Research Institute (LRI) is home to Cleveland Clinic's laboratory, translational and clinical research. Its mission is to promote human health by investigating in the laboratory and the clinic the causes of disease and discovering novel approaches to prevention and treatments; to train the next generation of biomedical researchers; and to foster productive collaborations with those providing clinical care. The LRI continues to make a major contribution to the advancement of human health. In 2013, LRI researchers published nearly 600 articles in high-impact biomedical journals (top 10% of all biomedical journals). LRI's total annual research expenditure was $248 million in 2013 (with $106 million in competitive federal funding). More than 2,000 people (including approximately 175 principal investigators, 200 postdoctoral fellows, and about 170 graduate students) in 13 departments work in research programs focusing on cardiovascular, cancer, neurologic, musculoskeletal, allergic and immunologic, eye, metabolic, and infectious diseases. The LRI has more than 700,000 square feet of lab, office, and Core Services space. LRI faculty oversee the curriculum and teach students enrolled in the Cleveland Clinic Lerner College of Medicine (CCLCM) of Case Western Reserve University – training the next generation of physician-scientists. Institute faculty also participate in multiple doctoral programs, including the Molecular Medicine PhD Program, which integrates traditional graduate training with an emphasis on human diseases. The LRI is a significant source of commercial property, generating 61 invention disclosures, 5 licenses, and 38 patents in 2013.
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