HIV drug plus blood vessel growth-blockers could halt metastasis
Breast cancer cells can lay the groundwork for their own spread throughout the body by coaxing cells within lymphatic vessels to send out tumor-welcoming signals, according to a new report by Johns Hopkins scientists.
Writing in the Sept. 2 issue of Nature Communications, the researchers describe animal and cell-culture experiments that show increased levels of so-called signaling molecules released by breast cancer cells. These molecules cause lymphatic endothelial cells (LECs) in the lungs and lymph nodes to produce proteins called CCL5 and VEGF. CCL5 attracts tumor cells to the lungs and lymph nodes, and VEGF increases the number of blood vessels and makes them more porous, allowing tumor cells to metastasize and infiltrate the lungs.
In the same report, the researchers say maraviroc, a drug already approved for treating HIV infection, blocked the siren call of CCL5 in tests on animals and cells and prevented tumor spread (metastasis). Additional experiments using a combination of maraviroc and a drug that blocks the VEGF protein suggest that the treatment duo could be an effective way to prevent metastatic disease in human breast cancer patients, according to the researchers.
Because the anti-retroviral drug maraviroc has already been approved by the U.S. Food and Drug Administration and has been shown safe for long term, oral use, it could be tested in clinical trials sooner rather than later, says Aleksander Popel, Ph.D., a professor in the Department of Biomedical Engineering at the Johns Hopkins University School of Medicine and member of the Johns Hopkins Kimmel Cancer Center.
"It was surprising to find that LECs can play such an active and significant role in tumor spread." Popel noted. "Conventionally, lymphatic vessels are regarded mainly as passive conduits through which tumor cells spread from the primary tumor and eventually metastasize," he said. "However, we now know that lymphatic vessels enable metastasis, and other studies also show that they play an important role in whether or not immune cells recognize and attack cancer cells."
Popel and colleagues traced the influence of tumor signaling on LECs in cell cultures and in mice. Breast cancer cells were bathed in a nutrient-rich liquid, and, as the cancer cells grew, the investigators detected secretions of a signaling molecule called interleukin-6 (IL6) in the liquid.
Mice that were injected with the IL6-containing liquid experienced a continual rise in CCL5 levels in blood samples for several weeks. Nine of 10 tumor-bearing mice injected with the IL6-laden liquid developed metastases five weeks later. Only two of 10 mice, exposed to the liquid and given a combination of maraviroc and a VEGF-blocking drug, developed metastases.
Because maraviroc blocks the actions of CCL5, it could be delivered, along with standard chemotherapy, right after surgically removing a tumor in a bid to prevent any leftover circulating tumor cells from finding a new metastatic niche in the body, Popel says.
"However, IL6-secreting tumors could be laying the groundwork for metastasis much earlier than surgery occurs in a patient," he said. "To prevent metastatic sites from taking root, we could administer drugs that block IL6 before surgery."
The study did not address when or how to remove lymph node tissue surgically, as is often done as part of breast cancer treatment, but Popel and colleagues hope to explore the issue in future studies.
Other researchers on the paper include Esak Lee, the first author, and Niranjan Pandey of the Department of Biomedical Engineering, Johns Hopkins University School of Medicine and Elana Fertig, Kideok Jin, and Saraswati Sukumar of the Johns Hopkins Kimmel Cancer Center.
Funding for the study was provided by the National Institutes of Health's National Cancer Institute (R01 CA138264) and the Safeway Foundation for Breast Cancer.
Johns Hopkins Medicine (JHM), headquartered in Baltimore, Maryland, is a $7 billion integrated global health enterprise and one of the leading academic health care systems in the United States. JHM unites physicians and scientists of the Johns Hopkins University School of Medicine with the organizations, health professionals and facilities of The Johns Hopkins Hospital and Health System. JHM's vision, "Together, we will deliver the promise of medicine," is supported by its mission to improve the health of the community and the world by setting the standard of excellence in medical education, research and clinical care. Diverse and inclusive, JHM educates medical students, scientists, health care professionals and the public; conducts biomedical research; and provides patient-centered medicine to prevent, diagnose and treat human illness. JHM operates six academic and community hospitals, four suburban health care and surgery centers, and more than 35 Johns Hopkins Community Physicians sites. The Johns Hopkins Hospital, opened in 1889, has been ranked number one in the nation by U.S. News & World Report for 22 years of the survey's 25 year history, most recently in 2013. For more information about Johns Hopkins Medicine, its research, education and clinical programs, and for the latest health, science and research news, visit http://www.hopkinsmedicine.org
Vanessa Wasta, 410-614-2916, email@example.com
Amy Mone, 410-614-2915, firstname.lastname@example.org
Vanessa Wasta | Eurek Alert!
Shark Tagged by NSU’s Guy Harvey Research Institute Is Apparently Enjoying Time in Warm, Tropical Waters
30.03.2015 | Nova Southeastern University
Misuse of Sustainability Concept May Lead to Even More Toxic Chemical Materials
30.03.2015 | Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences
In an experiment at the Department of Energy's SLAC National Accelerator Laboratory, scientists precisely measured the temperature and structure of aluminum as...
The IPH presents a solution at HANNOVER MESSE 2015 to make ship traffic more reliable while decreasing the maintenance costs at the same time. In cooperation with project partners, the research institute from Hannover, Germany, has developed a sensor system which continuously monitors the condition of the marine gearbox, thus preventing breakdowns. Special feature: the monitoring system works wirelessly and energy-autonomously. The required electrical power is generated where it is needed – directly at the sensor.
As well as cars need to be certified regularly (in Germany by the TÜV – Technical Inspection Association), ships need to be inspected – if the powertrain stops...
When an earthquake hits, the faster first responders can get to an impacted area, the more likely infrastructure--and lives--can be saved.
The Atlantic overturning is one of Earth’s most important heat transport systems, pumping warm water northwards and cold water southwards. Also known as the Gulf Stream system, it is responsible for the mild climate in northwestern Europe.
Scientists now found evidence for a slowdown of the overturning – multiple lines of observation suggest that in recent decades, the current system has been...
Because they are regularly subjected to heavy vehicle traffic, emissions, moisture and salt, above- and underground parking garages, as well as bridges, frequently experience large areas of corrosion. Most inspection systems to date have only been capable of inspecting smaller surface areas.
From April 13 to April 17 at the Hannover Messe (hall 2, exhibit booth C16), engineers from the Fraunhofer Institute for Nondestructive Testing IZFP will be...
25.03.2015 | Event News
19.03.2015 | Event News
17.03.2015 | Event News
30.03.2015 | Press release
30.03.2015 | Life Sciences
30.03.2015 | Earth Sciences