NIH scientists find a potential new avenue for cancer therapies

December 19, 2011

Recent findings in mice suggest that blocking the production of small molecules produced in the body, known as epoxyeicosatrienoic acids (EETs), may represent a novel strategy for treating cancer by eliminating the blood vessels that feed cancer tumors. This research is the first to show that EETs work in concert with vascular endothelial growth factor (VEGF), a protein known to induce blood vessel growth. Together, EETs and VEGF promote metastasis, or the spread of cancer, by encouraging the growth of blood vessels that supply nutrients to cancer cells.

The research team comprised of scientists from the National Institute of Environmental Health Sciences (NIEHS), which is part of the National Institutes of Health, and several other institutions, published its data online in the Dec. 19 issue of The Journal of Clinical Investigation.

Preclinical research suggests that patients with a variety of vascular conditions, such as diabetes, hypertension, inflammation, stroke, and heart attack may benefit by increasing their EET levels, because the compounds cause blood vessels to dilate and reduce tissue inflammation and cell death. However, previous work has also demonstrated that EETs make tumor cells grow faster and cause them to migrate and become metastatic. Darryl Zeldin, M.D., NIEHS scientific director and author on the paper, said he believed that human metabolism has to achieve a certain harmony in regard to EETs.

"The body has to produce enough EETs to maintain a healthy cardiovascular system without promoting cancer. It has to balance the double-edged sword just right," Zeldin said.

To find out how EETs encourage the development of cancer, the team created two mice strains, one with high levels of EETs and one with low levels of EETs.

"The mice with higher EETs developed more metastatic tumors compared to the mice with lower EETs," Zeldin said. "Often, the tumor itself will produce more EETs, which can speed up tumor growth and its subsequent spread, but our analysis demonstrated that the EETs produced by the surrounding tissues encouraged tumor growth and migration."

Matthew Edin, Ph.D., a research fellow in Zeldin's group, is one of the authors on the paper and helped develop the mice strains. He said EETs directly lead to the creation of new blood vessels, also known as angiogenesis, which the cancer cells need in order to receive oxygen and nutrients to grow. He equated the process to what happens when a builder begins constructing a new housing development.

"One of the first things construction crews have to do is build the roads, so that materials and workers can be transported to the site," Edin said. "In cancer, EETs accelerate the road building, allowing the housing development to expand quickly."

According to Dipak Panigrahy, M.D., an author on the paper and a research associate at the Dana-Farber/Children's Hospital Cancer Center, Boston, EETs have a potent stimulatory effect promoting cancer growth and metastasis, a process that could be effectively inhibited using novel antagonists, such as EEZE, which are compounds that interfere with this pathway in mice. EEZE has not been approved for human use, and is only used for research.

"EEZE is structurally similar to EETs, but it blocks the effect of EETs and dramatically slows tumorigenesis," Panigrahy explained.

Mark Kieran, M.D., Ph.D., another author of this collaborative study and also from Dana-Farber, commented on the importance of the research.

"The identification of an old pathway studied for many years in cardiovascular disease has found a new role in regulating cancer growth and metastasis, the primary causes of cancer related deaths," he said. "With these findings, opportunities to better understand the underlying mechanisms that drive cancer, and thus the development of effective therapies for their treatment, moves one step closer to a reality."
-end-
Reference: Panigrahy D, Edin ML, Lee CR, Huang S, Bielenberg DR, Butterfield CE, Barnes CM, Mammoto A, Mammoto T, Luria A, Benny O, Chaponis DM, Dudley AC, Greene ER, Vergilio JA, Pietramaggiori G, Scherer-Pietramaggiori SS, Short SM, Seth M, Lih FB, Tomer KB, Yang J, Schwendener RA, Hammock BD, Falck JR, Manthati VL, Ingber DE, Kaipainen A, D'Amore PA, Kieran MW, Zeldin DC. 2011. Epoxyeicosanoids stimulate multiorgan metastasis and tumor dormancy escape in mice. J Clin Invest; doi:10.1172/JCI58128 [Online 19 December 2011]. The NIEHS supports research to understand the effects of the environment on human health and is part of NIH. For more information on environmental health topics, visit www.niehs.nih.gov. Subscribe to one or more of the NIEHS news lists (www.niehs.nih.gov/news/releases/newslist/index.cfm) to stay current on NIEHS news, press releases, grant opportunities, training, events, and publications.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

NIH...Turning Discovery Into Health

NIH/National Institute of Environmental Health Sciences

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.