It's a high-pressure environment within solid tumors. Abnormal blood and lymphatic vessels cause fluids to accumulate, and the uncontrolled proliferation of cancer cells within limited space leads to the buildup of what is called solid stress.
Both types of pressure can interfere with the effectiveness of anticancer treatments, but while strategies have been developed that reduce fluid pressures, little has been known about the impact of solid stress or potential ways to alleviate it. Now a Massachusetts General Hospital (MGH) research team has identified factors that contribute to solid stress within tumors, suggesting possible ways to alleviate it, and has developed a simple way to measure such pressures.
"Traditionally cancer research has focused on cancer cells and, more recently, on the biochemical microenvironment of tumors," says Rakesh Jain, PhD, director of the Steele Laboratory for Tumor Biology at MGH and senior author of the study in the Sept. 18 issue of Proceedings of the National Academy of Sciences. "Our work shows that the physical or mechanical microenvironment plays an equally important role in tumor progression and treatment resistance."
Jain and his colleagues have been leaders in understanding the impact of elevated fluid pressures that make it difficult for drugs to enter and permeate tumors. Their work showed that fluid pressures are relieved when antiangiogenesis drugs normalize the abnormal blood vessels characteristically found within solid tumors, improving the effectiveness of other anticancer therapies. But that approach can only work if vessels have not been squeezed shut by solid stress in surrounding tissues. In recent studies Jain's team showed that solid stress also increases the invasiveness of cancer cells.
The current study was designed to develop techniques that measure solid stress in tumors, to identify factors that contribute to the generation of this solid stress and to determine whether previously compressed blood vessels would open when stress-inducing components were depleted. Based on predictions from mathematical models, the MGH-based team developed a remarkably simple way to measure solid stress within tumor tissues.
In experiments using both tumors experimentally grown in mice and tumors removed from human patients, the researchers found that, when a solid tumor is cut in two, each segment begins to swell along the sliced surface, releasing stored solid stress. In contrast, when a sample of normal tissue is cut in two, the separated halves of tissue retain their size and shape (links to video files below). Measuring the extent of shape relaxation along with other mechanical properties of tumor tissue enabled calculation of the amount of solid stress within a tumor sample.
Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $750 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, reproductive biology, systems biology, transplantation biology and photomedicine. In July 2012, MGH moved into the number one spot on the 2012-13 U.S. News & World Report list of "America's Best Hospitals."
Sue McGreevey | EurekAlert!
Multi-year study finds 'hotspots' of ammonia over world's major agricultural areas
17.03.2017 | University of Maryland
Diabetes Drug May Improve Bone Fat-induced Defects of Fracture Healing
17.03.2017 | Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
24.03.2017 | Materials Sciences
24.03.2017 | Physics and Astronomy
24.03.2017 | Physics and Astronomy