Navigation Links
Researchers isolate protein domain linked to tumor progression
Date:2/17/2009

Troy, N.Y. When a promising cancer drug reached clinical trials in the 1990s, researchers were disappointed by the debilitating side effects that limited the trials. The drug inhibited a family of enzymes known as matrix metalloproteinases (MMPs). Now, researchers at Rensselaer Polytechnic Institute have shown that creating drugs that inactivate a different part of the MMP enzyme could have the capacity to target the tumor without the damaging side effects. Their findings, which hold promise for improved cancer therapies, were published Feb. 5 in the online Early Edition of the Proceedings of the National Academy of Sciences (PNAS).

"The failure of the clinical trials suggest that the proteinases were not only involved in the pathology of the disease, but also in maintaining the normal health of the patient," said Andrea Page-McCaw, assistant professor of biology at Rensselaer and the corresponding author of the study. Page-McCaw and her colleagues, including senior research specialist Bernadette M. Glasheen and undergraduate biology student Aasish Kabra, set out to determine the functions of different parts of an MMP enzyme. These parts, known as domains, usually correlate to a specific protein function. Inactivating one domain within a protein can often have significant and unknown consequences.

To determine MMP domain function, the researchers used a simple model organism, the common fruit fly. Unlike mouse and other mammal models that have 24 or more different and semi-redundant MMPs, the fly model has only two. This substantially simplifies the problem of understanding function of each domain, as there aren't so many other closely related proteins that can fill in if a domain on one is broken.

The researchers found that a domain known as the hemopexin domain was important for tissue invasion events. During tissue invasion, cells from one tissue invade into and usually move through another tissue, sometimes ending up in a completely different part of the body from where the tissue was formed. This pathway is similar to metastasis, where cancer cells spread from the original tumor to other sites in the body. Fly larvae missing the hemopexin domain of Mmp1 had highly distorted or absent head and wings. The growth of such body parts requires tissue invasion to move the cells to the right place in the animal. These abnormalities indicate that a hemopexin domain is needed for tissue invasion in fly development, and possibly in cancer metastasis, according to Page-McCaw.

The other primary domain in MMPs, the catalytic domain, is considered the business part of the enzyme, as it is where MMPs break up or destroy other proteins. The catalytic domain was extensively targeted by pharmaceutical companies in efforts to block MMP function in cancer. The researchers found that in flies, like in patients, blocking or removing the catalytic domain caused many different kinds of problems, beyond simply failures of tissue invasion. When the catalytic domain was removed, the larvae could not grow normally because they were unable to make necessary and basic developmental changes in their exoskeletons. The findings shed light on why inhibiting the catalytic domain in the drug trials would have both the favorable impact of stopping tissue invasion and unfavorable impact of significant side effects. In the future, inhibiting only the hemopexin domain could be a method to inhibit tissue invasion without inhibiting all other necessary MMP functions, Page-McCaw said.


'/>"/>

Contact: Gabrielle DeMarco
demarg@rpi.edu
518-276-6542
Rensselaer Polytechnic Institute
Source:Eurekalert

Related biology news :

1. CSHL researchers identify gene that helps plant cells keep communication channels open
2. Researchers identify gene linked to aggressive progression of liver cancer
3. Case Western Reserve researchers looking at light-induced toxins in air and water
4. McMaster researchers discover new mode of how diseases evolve
5. Researchers shed new light on connection between brain and loneliness
6. Texas researchers provide emissions data for livestock industry
7. Biodiversity itself begets a species cascade, researchers say
8. NYU Langone Medical Center researchers find micro RNA plays a key role in melanoma metastasis
9. While focusing on heart disease, researchers discover new tactic against fatal muscular dystrophy
10. NSF-funded workshops help young researchers teach science
11. Researchers observe evolution chain reaction
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/16/2016)... SAN FRANCISCO , June 16, 2016 /PRNewswire/ ... Market size is expected to reach USD ... report by Grand View Research, Inc. Technological proliferation ... and banking applications are expected to drive the ... ) , The development of ...
(Date:6/3/2016)... , June 3, 2016 ... Management) von Nepal ... und Lieferung hochsicherer geprägter Kennzeichen, einschließlich Personalisierung, ... führend in der Produktion und Implementierung von ... der Ausschreibung im Januar teilgenommen, aber Decatur ...
(Date:5/24/2016)... superior patient care by providing unparalleled technology to leaders of the medical imaging industry. ... recently added to the range of products distributed by Ampronix. Photo - ... ... ... ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... , June 23, 2016   EpiBiome , ... secured $1 million in debt financing from Silicon Valley ... up automation and to advance its drug development efforts, ... new facility. "SVB has been an incredible ... the services a traditional bank would provide," said Dr. ...
(Date:6/23/2016)... ... ... In a new case report published today in STEM CELLS Translational Medicine, ... after being treated for breast cancer benefitted from an injection of stem cells derived ... debilitating, frequent side effect of cancer treatment. , Lymphedema refers to the ...
(Date:6/23/2016)... 23, 2016 Andrew ... http://doi.org/10.17925/OHR.2016.12.01.22 Published recently in ... journal from touchONCOLOGY, Andrew D Zelenetz , ... cancer care is placing an increasing burden on ... biologic therapies. With the patents on many biologics ...
(Date:6/23/2016)... , ... June 23, 2016 , ... ... quality, regulatory and technical consulting, provides a free webinar on Performing ... July 13, 2016 at 12pm CT at no charge. , Incomplete investigations are ...
Breaking Biology Technology: