Navigation Links
Study identifies growth factor essential to the most common malignant pediatric brain tumor
Date:2/28/2013

A multi-institutional team led by Massachusetts General Hospital (MGH) researchers has identified a molecular pathway that appears to be essential for the growth and spread of medulloblastoma, the most common malignant brain tumor in children. In their report in the Feb. 28 issue of Cell, they show that blocking this pathway which involves interactions between tumor cells and the surrounding tissues leads to regression of all four molecular subtypes of medulloblastoma in several mouse models.

"Our finding that a pathway carrying signals from host cells to tumor cells via placental growth factor and its receptor neuropilin 1 is critical to the growth of medulloblastoma, regardless of molecular subtype, strongly supports evaluating antibodies against these proteins as a novel therapeutic approach to this pediatric cancer," says Rakesh K. Jain, PhD, director of the Steele Laboratory for Tumor Biology at MGH and corresponding author of the study.

A highly malignant tumor that originates in the cerebellum, medulloblastoma accounts for about 20 percent of all pediatric brain tumors and is ten times more common in children than in adults. While aggressive treatment with surgery, chemotherapy and radiation significantly improves patient survival, those treatments can have long-term developmental, behavioral, and neurological side effects, particularly in the youngest patients, making the need for less damaging therapies essential.

Impetus for the current investigation began with studies by Peter Carmeliet, MD, PhD, of the Vesalius Research Center in Belgium, a co-author of the current study. Carmeliet found that an antibody against placental growth factor (PlGF) could block angiogenesis in a number of adult tumors. Since PlGF, unlike other angiogenic proteins, is not required for normal postnatal development, Jain and his Steele Lab colleague Lei Xu, MD, PhD, proposed targeting PlGF as anti-angiogenic treatment for pediatric tumors. Matija Snuderl, MD, of the Steele Lab, a co-lead author of the current study, then found that PlGF was highly expressed in all types of medulloblastoma. Other members of Jain's team found that high expression of the P1GF receptor neuropilin 1 (Nrp1) was associated with poor survival in medulloblastoma patients.

To investigate mechanisms behind the potential role of PlGF in medulloblastoma, the MGH investigators collaborated with colleagues in the U.S., Belgium, Canada and Germany. They first confirmed that PlGF is expressed in patient samples of all subtypes of medulloblastoma and that expression of Nrp1 was more significant than that of PlGF's more common receptor, VEGFR1. Experiments in several mouse models revealed that the presence of PlGF is essential for the progression of medulloblastoma and that treatment with several antibodies against the growth factor reduced tumor growth and spread, increasing animal survival even without substantially inhibiting angiogenesis

The researchers were surprised to find that most PlGF was produced by surrounding supportive tissue called stroma and not by the tumor cells. Further investigation revealed that release of the developmental protein Shh (sonic hedgehog) by tumor cells induces expression in nearby stromal cells of PlGF, which then binds to the Nrp1 receptor on tumor cells, leading to further tumor growth. The authors note that therapies that block the interaction between PlGF and Nrp1 are less likely to lead to treatment resistance than are therapies directly targeting mutations that drive tumor growth.

"The importance of tumor-stromal interactions has been recognized for decades, especially the formation of new blood vessels to supply tumors," says Jain, the Cook Professor of Radiation Oncology (Tumor Biology) at Harvard Medical School. "Our discovery of an entirely different way that tumor-stromal interactions drive cancer progression supports the exciting possibility that targeting that pathway in medulloblastoma could be more broadly effective with fewer side effects for patients. Antibodies against both PlGF and Nrp1 have been developed and tested in adult patients. There is hope that they could be safe in pediatric patients, but that needs to be established in clinical trials."


'/>"/>

Contact: Katie Marquedant
kmarquedant@partners.org
617-726-0337
Massachusetts General Hospital
Source:Eurekalert  

Related medicine news :

1. Study finds diabetes does not increase risk of total knee surgical complications
2. Too Much Sitting Could Court Diabetes, Study Finds
3. UCLA study could explain why some people get zits and others dont
4. Babies Born to Obese Women Show Thicker Arteries: Study
5. Siblings Death May Boost Your Own Risk of Dying From Heart Attack: Study
6. Costs of ER Visits Vary in U.S., Study Finds
7. Einstein receives $3 million to study impact of soccer heading on the brain
8. Retailers should re-size maternity wear for women throughout their pregnancies, MU study finds
9. More Younger Women Diagnosed With Advanced Breast Cancer: Study
10. Dog Study Raises Prospect of Biological Pacemaker for Humans
11. Surgery and radiation improve survival for metastatic gastric cancer patients, Moffitt study shows
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Study identifies growth factor essential to the most common malignant pediatric brain tumor
(Date:2/26/2017)... ... February 26, 2017 , ... Functional imaging data supports ... a study released today at the 1st Pan American Parkinson’s and Movement Disorders ... be effective in improving cognitive function in PD patients. This study, led by ...
(Date:2/24/2017)... ... February 24, 2017 , ... HealthPostures, ... Go. Core benefits and advantages built into the home office sit stand solution ... and feel. Ability to gain the benefits embedded in the TaskMate Go are ...
(Date:2/24/2017)... ... February 24, 2017 , ... WHAT: , The ... recognition opportunities as well as advocacy for the state and region‘s technology businesses, ... 23. The Council's Innovation Forecast event highlights innovation throughout the region from ...
(Date:2/24/2017)... ... ... The Smart Machine Age is here, and it’s disrupting everything. Not only could ... in the United States may be taken over by technology in the next five ... steamrolls over colleagues is drawing to a close. Success will belong to those who ...
(Date:2/24/2017)... (PRWEB) , ... February 24, 2017 , ... Healthcare ... The Medical Center at Craig Ranch building at 8080 State Highway 121, Suite 210, ... District with easy access to Highway 121. , As the practice has grown, the ...
Breaking Medicine News(10 mins):
(Date:2/27/2017)... 2017   Royal Philips (NYSE: ... in health technology, today announced 510(k) clearance from ... market its ElastQ Imaging capability, further expanding the ... ElastQ Imaging enables simultaneous imaging of tissue and ... the diagnosis of various liver conditions. With ElastQ ...
(Date:2/27/2017)... 2017  RegeneRx Biopharmaceuticals, Inc. (OTCQB: RGRX) ("the ... focused on tissue protection, repair and regeneration, today ... Ltd., received a positive response from the U.S. ... for RGN-137 to treat epidermolysis bullosa ("EB"). RGN-137 ... Thymosin beta 4 ("Tß4") as the active pharmaceutical ...
(Date:2/27/2017)... , Feb. 27, 2017  CTI BioPharma Corp. (CTI BioPharma) ... Adam Craig , M.D., Ph.D., as President and Chief Executive ... March 20, 2017. Dr. Craig succeeds Richard Love , ... the company,s Board of Directors.  Dr. Craig has over 20 ... both the US and Europe . ...
Breaking Medicine Technology: