Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

‘Prepped’ by tumor cells, lymphatic cells encourage breast cancer cells to spread

03.09.2014

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.

... more about:
»Cancer »Medicine »VEGF »lungs »lymph »lymphatic »metastasis »metastatic

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

Media Contacts:

Vanessa Wasta, 410-614-2916, wasta@jhmi.edu

Amy Mone, 410-614-2915, amone@jhmi.edu

Vanessa Wasta | Eurek Alert!

Further reports about: Cancer Medicine VEGF lungs lymph lymphatic metastasis metastatic

More articles from Life Sciences:

nachricht Identifying drug targets for leukaemia
02.05.2016 | The Hong Kong Polytechnic University

nachricht A cell senses its own curves: New research from the MBL Whitman Center
29.04.2016 | Marine Biological Laboratory

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: 2+1 is Not Always 3 - In the microworld unity is not always strength

If a person pushes a broken-down car alone, there is a certain effect. If another person helps, the result is the sum of their efforts. If two micro-particles are pushing another microparticle, however, the resulting effect may not necessarily be the sum their efforts. A recent study published in Nature Communications, measured this odd effect that scientists call “many body.”

In the microscopic world, where the modern miniaturized machines at the new frontiers of technology operate, as long as we are in the presence of two...

Im Focus: Tiny microbots that can clean up water

Researchers from the Max Planck Institute Stuttgart have developed self-propelled tiny ‘microbots’ that can remove lead or organic pollution from contaminated water.

Working with colleagues in Barcelona and Singapore, Samuel Sánchez’s group used graphene oxide to make their microscale motors, which are able to adsorb lead...

Im Focus: ORNL researchers discover new state of water molecule

Neutron scattering and computational modeling have revealed unique and unexpected behavior of water molecules under extreme confinement that is unmatched by any known gas, liquid or solid states.

In a paper published in Physical Review Letters, researchers at the Department of Energy's Oak Ridge National Laboratory describe a new tunneling state of...

Im Focus: Bionic Lightweight Design researchers of the Alfred Wegener Institute at Hannover Messe 2016

Honeycomb structures as the basic building block for industrial applications presented using holo pyramid

Researchers of the Alfred Wegener Institute (AWI) will introduce their latest developments in the field of bionic lightweight design at Hannover Messe from 25...

Im Focus: New world record for fullerene-free polymer solar cells

Polymer solar cells can be even cheaper and more reliable thanks to a breakthrough by scientists at Linköping University and the Chinese Academy of Sciences (CAS). This work is about avoiding costly and unstable fullerenes.

Polymer solar cells can be even cheaper and more reliable thanks to a breakthrough by scientists at Linköping University and the Chinese Academy of Sciences...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

The “AC21 International Forum 2016” is About to Begin

27.04.2016 | Event News

Soft switching combines efficiency and improved electro-magnetic compatibility

15.04.2016 | Event News

Grid-Supportive Buildings Give Boost to Renewable Energy Integration

12.04.2016 | Event News

 
Latest News

Identifying drug targets for leukaemia

02.05.2016 | Life Sciences

Clay nanotube-biopolymer composite scaffolds for tissue engineering

02.05.2016 | Materials Sciences

NASA's Fermi Telescope helps link cosmic neutrino to blazar blast

02.05.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>