The findings are published in this week's online Early Edition of the Proceedings of the National Academy of Sciences.
Roughly 90 percent of all cancer deaths are due to metastasis – the disease spreading from the original tumor site to multiple, distant tissues and finally overwhelming the patient's body. Lymph vessels are often the path of transmission, with circulating tumor cells lodging in the lymph nodes – organs distributed throughout the body that act as immune system garrisons and traps for pathogens and foreign particles.
The researchers, led by principal investigator Judith A. Varner, PhD, professor of medicine at UC San Diego Moores Cancer Center, found that a protein growth factor expressed by tumors called VEGF-C activates a receptor called integrin á4â1 on lymphatic vessels in lymph node tissues, making them more attractive and sticky to metastatic tumor cells.
"One of the most significant features of this work is that it highlights the way that tumors can have long-range effects on other parts of the body, which can then impact tumor metastasis or growth," said Varner.
Varner said á4â1 could prove to be a valuable biomarker for measuring cancer risk, since increased levels of the activated protein in lymph tissues is an indirect indicator that an undetected tumor may be nearby.
She said whole-body imaging scans of the lymphatic network might identify problem areas relatively quickly and effectively. "The idea is that a radiolabeled or otherwise labeled anti-integrin á4â1 antibody could be injected into the lymphatic circulation, and it would only bind to and highlight the lymphatic vessels that have been activated by the presence of a tumor."
Varner noted that á4â1 levels correlate with metastasis – the higher the level, the greater the chance of the cancer spreading. With additional research and clinical studies, doctors could refine treatment protocols so that patients at higher risk are treated appropriately, but patients at lower or no risk of metastasis are not over-treated.
The researchers noted in their studies that it is possible to suppress tumor metastasis by reducing growth factor levels or by blocking activation of the á4â1 receptor. Varner said an antibody to VEGF-R3 is currently in Phase 1 clinical trials. An approved humanized anti-á4â1 antibody is currently approved for the treatment of multiple sclerosis and Crohn's disease. Varner said her lab at UC San Diego Moores Cancer Center is investigating the possibility of developing one for treating cancer.
Co-authors include Barbara Garmy-Susini, Christie J. Avraamides, Michael C. Schmid and Philippe Foubert, UC San Diego Moores Cancer Center; Jay S. Desgrosellier, UC San Diego Moores Cancer Center and UCSD Department of Pathology; Lesley G. Ellies, Scott R. Vanderberg, Brian Datnow, Huan-You Wang and David A. Cheresh, UCSD Department of Pathology; Andrew M. Lowy and Sarah L. Blair, UC San Diego Moores Cancer Center and UCSD Department of Surgery.
Funding for this research came, in part, from National Institutes of Health grants CA83133 and CA126820; Department of Defense grant W81XWH-06-1-052 and NIH-National Cancer Institute grant U54 CA119335.
Scott LaFee | EurekAlert!
Live probiotics can re-balance the gut microbiome and modify immune system response
20.11.2018 | Symprove
Purdue cancer identity technology makes it easier to find a tumor's 'address'
16.11.2018 | Purdue University
Max Planck researchers revel the nano-structure of molecular trains and the reason for smooth transport in cellular antennas.
Moving around, sensing the extracellular environment, and signaling to other cells are important for a cell to function properly. Responsible for those tasks...
Researchers at the University of New Hampshire have captured a difficult-to-view singular event involving "magnetic reconnection"--the process by which sparse particles and energy around Earth collide producing a quick but mighty explosion--in the Earth's magnetotail, the magnetic environment that trails behind the planet.
Magnetic reconnection has remained a bit of a mystery to scientists. They know it exists and have documented the effects that the energy explosions can...
Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.
Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...
Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.
In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...
On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.
19.11.2018 | Event News
09.11.2018 | Event News
06.11.2018 | Event News
20.11.2018 | Life Sciences
20.11.2018 | Life Sciences
20.11.2018 | Physics and Astronomy