Blocking angiogenesis to stop cancer growth and target other diseases

April 25, 2017 by Kathy Keatley Garvey, UC Davis
Researcher Amy Rand . Credit: Kathy Keatley Garvey

Newly published UC Davis research characterizing specific mechanisms involved in blocking angiogenesis, or the formation new blood vessels, has the potential to block cancer growth and target other diseases, researchers said today.

Earlier research by the Judah Folkman laboratory of Harvard Medical School showed that cutting off blood vessels that feed a cancerous tumor can stop its growth.

The seven-member research team—five from the Bruce Hammock laboratory of UC Davis—"characterized a novel lipid signaling molecule that can change fundamental biological processes involved in our health and disease," said lead author and researcher Amy Rand. "We've found that a novel product derived from the metabolism of omega-6 fatty acids stimulates angiogenesis, which may contribute to enhanced by providing tumors with oxygen and nutrients."

"As a highly regulated process, angiogenesis is critical for wound healing and development, but many diseases result in unregulated angiogenesis, including ," explained Rand, a postdoctoral fellow in the lab of Bruce Hammock, a distinguished professor who holds a joint appointment with UC Davis Department of Entomology and Nematology and the UC Davis Comprehensive Cancer Center. "We may be able to control angiogenesis to stimulate wound healing when necessary, but also block tumor growth in patients. Diseases that rely on angiogenesis may be able to be treated in part by changes in dietary lipid exposure or by controlling levels of these metabolites through enzyme inhibitors that block their formation."

The research, published April 10 in the Proceedings of the National Academy of Sciences (PNAS), explains, in part, why inhibiting the soluble epoxide hydrolase (sEH) in some systems is angiogenic whereas combining sEH inhibition with the inhibition of cyclooxygenase (COX) enzymes is dramatically antiangiogenic, which in turn may suppress tumor growth.

"There's uncertainty regarding the link between unsaturated fats and cancer, due to ongoing conflicts between scientific studies and insufficient data," Rand said. "Because of this, there is a major gap in our understanding of how these essential dietary fats affect our health. We used tools to detect and characterize unknown metabolites from omega-6 unsaturated fats and determined their effect on angiogenesis, to address at least a small part of this uncertainty by focusing on how these fats contribute to cancer tumor growth."

Hammock, who holds a joint appointment in the UC Davis Department of Entomology and Nematology and the UC Davis Comprehensive Cancer Center, said the research, titled "Cyclooxygenase-Derived Proangiogenic Metabolites of Epoxyeicosatrienoic Acids

Holds long term hope for cancer patients and those afflicted with heart, eye and other diseases. The team also included Christophe Morisseau, Bogdan Barnych, and Kin Sing Stephen Lee all of the UC Davis Department of Entomology and Nematology and UC Davis Comprehensive Cancer Center; Tomas Cajka of the UC Davis Genome Center; and Dipak Panigraphy of Harvard Medical School. Lee is now an assistant professor at Michigan State University.

"Pro and anti-angiogenic therapy can potentially help millions of people worldwide in various diseases such as heart, ulcers, eye and cancer as first demonstrated by Dr. Judah Folkman and his colleagues," said Panigraphy, formerly of the Hammock lab and now with the Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Harvard Medical School, and the school's Department of Pathology.

"While the COX and sEH pathways can be targeted with drugs, their interaction is poorly understood," Panigraphy said. "These studies by Rand et al demonstrate for the first time new specific mechanisms whereby targeting the sEH pathway can be both pro- and anti-angiogenic and has the potential to help patients with devastating diseases such as in the eye and cancer where blocking angiogenesis is desired."

Rand, who received her doctorate in chemistry from the University of Toronto, Canada, in 2013, the same year she joined Hammock's biological analytical chemistry lab, said she's "always been interested in research that combines chemistry and biology to enhance our understanding of human health."

Future work? "We aim to understand the direct involvement of these omega-6 fatty acid metabolites with cancer tumor growth and metastasis."

Rand last year received the $100,000 Judah Folkman Fellowship for Angiogenesis Research from the American Association for Cancer Research. She won the highly competitive international award for her proposal, "Regulation of Cancer Angiogenesis from the Metabolism of Epoxy Omega-6 Fats." Rand joined Hammock's biological analytical chemistry lab in 2013 and was a fellow on the Oncogenic Signals and Chromosome Biology T32 Training Grant, UC Davis Department of Microbiology and Molecular Genetics.

The late Judah Folkman (1933-2008), a Harvard Medical School professor considered the father of angiogenesis research, "is best known for pioneering the concept of blocking angiogenesis (the development of blood vessels) to control cancer growth," Hammock said. "This concept has resulted in a number of anti-cancer drugs and has had a major impact on cancer treatment. Of course, blood vessel development is also critical for survival."

Folkman discovered that cutting off the that feed the tumor can stop cancer tumor growth. His revolutionary work has led to the discovery of a number of therapies based on inhibiting or stimulating neovascularization. Inhibitors of the sEH pathway are moving toward human trials to control neuropathic pain, but if combined with nonsteroidal anti-inflammatory drugs can block tumor growth by blocking . So Dr. Sung Hee Hwang combined inhibitors of both pathways into one molecule which is being investigated in cancer models at the UC Davis Cancer Center by Dr. Paul Henderson and Northwestern University Medical School by Dr. Guang-yu Yang.

Explore further: Fatty acid metabolite shows promise against cancer in mice

More information: Amy A. Rand et al. Cyclooxygenase-derived proangiogenic metabolites of epoxyeicosatrienoic acids, Proceedings of the National Academy of Sciences (2017). DOI: 10.1073/pnas.1616893114

Related Stories

Fatty acid metabolite shows promise against cancer in mice

April 2, 2013
A team of UC Davis scientists has found that a product resulting from a metabolized omega-3 fatty acid helps combat cancer by cutting off the supply of oxygen and nutrients that fuel tumor growth and spread of the disease.

New combination drug controls tumor growth and metastasis in mice

July 15, 2014
Researchers at UC Davis, University of Massachusetts and Harvard Medical School have created a combination drug that controls both tumor growth and metastasis. By combining a COX-2 inhibitor, similar to Celebrex, and an epoxide ...

Suppressing vasculogenic mimicry in breast cancer

March 30, 2017
An article published in Experimental Biology and Medicine (Volume 242, Issue 6, March, 2017) identifies a new signaling pathway involved in breast cancer cell growth. The study, led by Dr. Chan-Wha Kim, from the Department ...

New target for the fight against cancer as a result of excessive blood vessel formation

August 1, 2013
New blood vessel formation (angiogenesis) stimulates the growth of cancer and other diseases. Anti-angiogenic inhibitors slow down cancer growth by disrupting the blood supply to the tumor. To date, the success of these treatments ...

Researchers find key mechanism that causes neuropathic pain

July 7, 2015
Scientists at the University of California, Davis, have identified a key mechanism in neuropathic pain. The discovery could eventually benefit millions of patients with chronic pain from trauma, diabetes, shingles, multiple ...

Morphine blocks tumor growth

July 28, 2010
Current research suggests that taking morphine can block new blood vessel and tumor growth. The related report by Koodie et al, "Morphine suppresses tumor angiogenesis through a HIF1α/p38MAPK pathway," appears in the ...

Recommended for you

Team develops new way to grow blood vessels

August 17, 2018
Formation of new blood vessels, a process also known as angiogenesis, is one of the major clinical challenges in wound healing and tissue implants. To address this issue, researchers from Texas A&M University have developed ...

New imaging technique can spot tuberculosis infection in an hour

August 16, 2018
Guided by glowing bacteria, researchers have devised an imaging technique that can diagnose live tuberculosis in an hour and help monitor the efficacy of treatments. That's particularly critical because many TB strains have ...

Obesity, infertility and oxidative stress in mouse egg cells

August 16, 2018
Excessive body fat is associated with negative effects on female fertility and pregnancy. In mice, maternal obesity impairs proper development of egg precursor cells called oocytes. In a recent paper published in Molecular ...

Research shows it's possible to reverse damage caused by aging cells

August 15, 2018
What's the secret to aging well? University of Minnesota Medical School researchers have answered it- on a cellular level.

This matrix delivers healing stem cells to injured elderly muscles

August 15, 2018
A car accident leaves an aging patient with severe muscle injuries that won't heal. Treatment with muscle stem cells from a donor might restore damaged tissue, but doctors are unable to deliver them effectively. A new method ...

Male tobacco smokers have brain-wide reduction of CB1 receptors

August 15, 2018
Chronic, frequent tobacco smokers have a decreased number of cannabinoid CB1 receptors, the "pot receptor", when compared with non-smokers, reports a study in Biological Psychiatry.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.