Featured Research

from universities, journals, and other organizations

Study uncovers enzyme's double life, critical role in cancer blood supply

Date:
March 4, 2013
Source:
University of Vermont
Summary:
Studied for decades for their essential role in making proteins within cells, several amino acids known as tRNA synthetases were recently found to have an unexpected -- and critical -- additional role in cancer metastasis. Researchers determined that threonyl tRNA synthetase leads a "double life," regulating a pathway used by invasive cancers to induce the formation of new blood vessels, and a new food supply to sustain their growth.

(From left) Adam Mirando, Ph.D., postdoctoral fellow in biochemistry; Tamara Williams, Ph.D., lecturer in nursing and a postdoctoral fellow in pharmacology; Christopher Francklyn, Ph.D., professor of biochemistry; and Karen Lounsbury, Ph.D., professor of pharmacology.
Credit: Photo by Ed Neuert

Studied for decades for their essential role in making proteins within cells, several amino acids known as tRNA synthetases were recently found to have an unexpected -- and critical -- additional role in cancer metastasis in a study conducted collaboratively in the labs of Karen Lounsbury, Ph.D., University of Vermont professor of pharmacology, and Christopher Francklyn, Ph.D., UVM professor of biochemistry. The group determined that threonyl tRNA synthetase (TARS) leads a "double life," functioning as a critical factor regulating a pathway used by invasive cancers to induce angiogenesis -- the formation of new blood vessels -- and a new food supply to sustain their growth.

The teams' research was published online February 21, 2013 in Nature Scientific Reports.

According to Tamara Williams, Ph.D., first author on the study, a lecturer in nursing and postdoctoral fellow in pharmacology at UVM, cancerous tumors quickly outgrow their local blood supply. When they do, the cancer cells send out signals, TARS is secreted, and the angiogenesis process is initiated.

"In our study, we showed that TARS, once thought to only function in the housekeeping role of protein synthesis within cells, 'moonlights' as a secreted signaling agent in the endothelial cells that line vessels, in response to factors commonly produced by cancer cells," says Williams.

The study's in vivo model of angiogenesis was performed using a chick chorioallantoic membrane assay. This experiment utilizes the vascular membrane that surrounds a ten-day-old chicken embryo, which is removed from its shell. Williams and her research teammates placed small pieces of surgical sponges on the surface of the membrane and added compounds, including TARS, to the sponges. The researchers took images of the sponges and surrounding tissues every 24 hours for three days and then analyzed the images to assess the impact of the compounds on local blood vessel development around the sponge. Their test determined whether the compound was angiogenic (creates new blood vessels), had no effect, or was angiostatic (inhibits blood vessel development). Using this assay, the group was able to demonstrate that TARS prompts angiogenesis by increasing the directional movement, or migration, of vessel cells towards the cancer cell signals. The group's research also showed that a potent inhibitor of TARS activity -- called inhibitor BC194 -- blocked its induction of angiogenesis.

"The implications of these novel and surprising findings are substantial for the cancer research community and include potential opportunities to develop new, early, and sensitive diagnostics," Williams says.

"Commercially, compounds that reduce TARS could be used to stop angiogenesis in cancer, compounds that increase TARS could promote angiogenesis, and a laboratory blood test for TARS could serve as a diagnostic for progression in certain cancers," says Kerry Swift, M.S., technology licensing officer in the UVM Office of Technology Commercialization.

Williams adds that the anti-angiogenic activity of the potent inhibitor of TARS paves the way for new therapeutics to block tumor growth and metastasis by stopping TARS-induced angiogenesis.

"These types of therapeutics could be used in combination with other treatments that target and kill cancer cells as part of a personalized cancer medicine approach to treat patients with greater success," she says.

On April 22, 2013, Francklyn will present a poster session on this research, titled "Mode of Action of Bioactive Natural Products," at the annual American Society for Biochemistry and Molecular Biology meeting in Boston, Mass. Lounsbury will present the project at the American Association for Cancer Research meeting, which takes place April 6 to 10, 2013 in Washington, D.C.


Story Source:

The above story is based on materials provided by University of Vermont. The original article was written by Jennifer Nachbur. Note: Materials may be edited for content and length.


Journal Reference:

  1. Tamara F. Williams, Adam C. Mirando, Barrie Wilkinson, Christopher S. Francklyn, Karen M. Lounsbury. Secreted Threonyl-tRNA synthetase stimulates endothelial cell migration and angiogenesis. Scientific Reports, 2013; 3 DOI: 10.1038/srep01317

Cite This Page:

University of Vermont. "Study uncovers enzyme's double life, critical role in cancer blood supply." ScienceDaily. ScienceDaily, 4 March 2013. <www.sciencedaily.com/releases/2013/03/130304211534.htm>.
University of Vermont. (2013, March 4). Study uncovers enzyme's double life, critical role in cancer blood supply. ScienceDaily. Retrieved July 31, 2014 from www.sciencedaily.com/releases/2013/03/130304211534.htm
University of Vermont. "Study uncovers enzyme's double life, critical role in cancer blood supply." ScienceDaily. www.sciencedaily.com/releases/2013/03/130304211534.htm (accessed July 31, 2014).

Share This




More Health & Medicine News

Thursday, July 31, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Health Insurers' Profits Slide

Health Insurers' Profits Slide

Reuters - Business Video Online (July 30, 2014) Obamacare-related costs were said to be behind the profit plunge at Wellpoint and Humana, but Wellpoint sees the new exchanges boosting its earnings for the full year. Fred Katayama reports. Video provided by Reuters
Powered by NewsLook.com
Concern Grows Over Worsening Ebola Crisis

Concern Grows Over Worsening Ebola Crisis

AFP (July 30, 2014) Pan-African airline ASKY has suspended all flights to and from the capitals of Liberia and Sierra Leone amid the worsening Ebola health crisis, which has so far caused 672 deaths in Guinea, Liberia and Sierra Leone. Duration: 00:43 Video provided by AFP
Powered by NewsLook.com
At Least 20 Chikungunya Cases in New Jersey

At Least 20 Chikungunya Cases in New Jersey

AP (July 30, 2014) At least 20 New Jersey residents have tested positive for chikungunya, a mosquito-borne virus that has spread through the Caribbean. (July 30) Video provided by AP
Powered by NewsLook.com
Xtreme Eating: Your Daily Caloric Intake All On One Plate

Xtreme Eating: Your Daily Caloric Intake All On One Plate

Newsy (July 30, 2014) The Center for Science in the Public Interest released its 2014 list of single meals with whopping calorie counts. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

    Environment News

    Technology News



    Save/Print:
    Share:

    Free Subscriptions


    Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

    Get Social & Mobile


    Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

    Have Feedback?


    Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
    Mobile: iPhone Android Web
    Follow: Facebook Twitter Google+
    Subscribe: RSS Feeds Email Newsletters
    Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins