Featured Research

from universities, journals, and other organizations

Study Fishes Out New Role For Prostaglandins

Date:
January 2, 2006
Source:
Vanderbilt University Medical Center
Summary:
A new study by Vanderbilt researchers reveals that prostaglandins help choreograph the intricate cell movements during early embryonic development in zebrafish, highlighting how perturbations in this pathway might influence human development and the spread of cancer. The results also may point to new molecular targets for cancer prevention therapies. The findings are published in the January 1 edition of the journal Genes and Development.

From left, Yong Cha, a graduate student, Raymond N. DuBois, M.D., Ph.D., and Lilianna Solnica-Krezel, Ph.D., take a closer look at some of the zebrafish they are studying. (hoto by Dana Johnson)

Prostaglandins – the fat-derived compounds linked to pain, inflammation, reproduction and cancer – can add another biological function to their extensive catalog.

Related Articles


A new study by Vanderbilt researchers reveals that prostaglandins help choreograph the intricate cell movements during early embryonic development in zebrafish, highlighting how perturbations in this pathway might influence human development and the spread of cancer. The results also may point to new molecular targets for cancer prevention therapies.

The findings, published January 1 in the journal Genes and Development, result from a cross-campus collaboration between the labs of Raymond DuBois, M.D., Ph.D., director of the Vanderbilt-Ingram Cancer Center and B.F. Byrd Jr. Professor of Molecular Oncology, and Lilianna Solnica-Krezel, Ph.D., professor of Biological Sciences.

Early in development, vertebrate embryos consist of one layer of cells. These simple embryos must go through a complex reorganization called gastrulation to establish the three primitive layers from which all adult tissues develop – the innermost layer (endoderm), which forms the gut and associated digestive organs; the middle layer (mesoderm), which develops into muscle, bone and cardiovascular organs, and the outer layer (ectoderm), which becomes the skin and nervous system.

"The body is a tube in a tube in a shell," Solnica-Krezel explained. "Before gastrulation, all of these prospective tubes are at the surface of the embryo. Gastrulation puts these different tissue precursors inside the embryo and gives them a proper shape."

But little is known about the chemical signals that cause these cells to move. Previous studies in mice and zebrafish suggested that prostaglandins were important in development. Mice lacking an enzyme that synthesizes prostaglandin had numerous developmental defects, but the true effects of prostaglandins on the embryo were likely obscured by maternal prostaglandin production.

Because they develop outside the mother and are transparent, zebrafish embryos provide a unique model in which to examine prostaglandin's role in development.

Yong Cha, a graduate student in DuBois' lab and first author on the study, established a collaboration with zebrafish researcher Solnica-Krezel to study this process.

The researchers inhibited the production of a specific type of prostaglandin, PGE2, in zebrafish embryos and examined their development.

In embryos treated with the inhibitor, gastrulation was arrested or slowed down significantly. The resulting embryo was also shorter than an untreated embryo.

"What is spectacular," said Solnica-Krezel, "is that…if you just put some prostaglandin back in the culture medium, you rescue the phenotype."

In another set of embryos, the researchers blocked prostaglandin receptors, EP2 and EP4. Blocking the EP4 receptor caused defects similar to those associated with blocking PGE2 synthesis. When the researchers analyzed cell movement, they found that the shapes and trajectories of embryonic cells were normal – they simply moved much slower. This suggested that signaling through the EP4 receptor regulates the speed of cell movements during gastrulation.

The sluggish cell movements could have profound implications for development.

"Timing (in development) is really important," DuBois explains. "If you are traveling and have to get to the train station at a particular time, if you are too slow, you are going to miss the train. If you don't get on that part of the trip, that disturbs the whole agenda."

"Development synchronizes or orchestrates a myriad of events in the proper sequence (lots of trains)," said Solnica-Krezel, "and sometimes one train wreck can halt the entire process."

While 'bad timing' during development can spell the end for an embryo, finding ways to exploit this pathway could have beneficial effects in cancer cells.

"The pathways important for regulating development are also dysregulated in cancer," said DuBois, who studies prostaglandin signaling in colon cancer. Knowing how prostaglandins regulate cell movement in development can help cancer researchers determine how cancer cells spread throughout the body, or metastasize – and how to stop the process. DuBois previously found that adding PGE2 to cultured cancer cells causes them to move much more rapidly.

"We've been able to show that some genes in this pathway are really important for cancer cells to spread to the liver," he said. "Eventually, we may be able to find a way to attack this pathway and prevent metastatic spread of colon cancer."

Scientists have known that people who take aspirin, a drug that inhibits prostaglandin synthesis, have about a 50 percent reduction in their risk of getting colon cancer, DuBois explained.

"We've been on a quest for the last 10 years to understand why such a simple drug leads to such a significant reduction in cancer risk," he said. "There are several parts to that puzzle. This (finding) may be one piece."

Zebrafish models may seem like a step back from the more traditional mouse models used to study cancer. But zebrafish, which develop quickly, are inexpensive and easy to manipulate, could actually aid in the discovery of new cancer drugs.

"If you could use the zebrafish intelligently to screen for these drugs, it might really speed up the drug discovery process and give us some early clues about the effects we may see in humans," DuBois said.

###

Other authors on the study were Seok-Hyung Kim and Diane Sepich in the Solnica-Krezel group, and F. Gregory Buchanan in the DuBois group. The research was supported by grants from the National Institutes of Health, the T.J. Martell Foundation, the National Colorectal Cancer Research Alliance and the Zebrafish Initiative funded by the Vanderbilt University Academic Venture Capital Fund.


Story Source:

The above story is based on materials provided by Vanderbilt University Medical Center. Note: Materials may be edited for content and length.


Cite This Page:

Vanderbilt University Medical Center. "Study Fishes Out New Role For Prostaglandins." ScienceDaily. ScienceDaily, 2 January 2006. <www.sciencedaily.com/releases/2006/01/060102104706.htm>.
Vanderbilt University Medical Center. (2006, January 2). Study Fishes Out New Role For Prostaglandins. ScienceDaily. Retrieved October 25, 2014 from www.sciencedaily.com/releases/2006/01/060102104706.htm
Vanderbilt University Medical Center. "Study Fishes Out New Role For Prostaglandins." ScienceDaily. www.sciencedaily.com/releases/2006/01/060102104706.htm (accessed October 25, 2014).

Share This



More Health & Medicine News

Saturday, October 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

IKEA Desk Converts From Standing to Sitting With One Button

IKEA Desk Converts From Standing to Sitting With One Button

Buzz60 (Oct. 24, 2014) IKEA is out with a new convertible desk that can convert from a sitting desk to a standing one with just the push of a button. Jen Markham explains. Video provided by Buzz60
Powered by NewsLook.com
Ebola Protective Suits Being Made in China

Ebola Protective Suits Being Made in China

AFP (Oct. 24, 2014) A factory in China is busy making Ebola protective suits for healthcare workers and others fighting the spread of the virus. Duration: 00:38 Video provided by AFP
Powered by NewsLook.com
WHO: Millions of Ebola Vaccine Doses by 2015

WHO: Millions of Ebola Vaccine Doses by 2015

AP (Oct. 24, 2014) The World Health Organization said on Friday that millions of doses of two experimental Ebola vaccines could be ready for use in 2015 and five more experimental vaccines would start being tested in March. (Oct. 24) Video provided by AP
Powered by NewsLook.com
Doctor in NYC Quarantined With Ebola

Doctor in NYC Quarantined With Ebola

AP (Oct. 24, 2014) An emergency room doctor who recently returned to the city after treating Ebola patients in West Africa has tested positive for the virus. He's quarantined in a hospital. (Oct. 24) Video provided by AP
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:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

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