Navigation Links
Blocking tumor-associated macrophages decreased glioblastoma's growth & extended survival in mice
Date:12/15/2013

An experimental drug that targets macrophages, a type of immune cells, in the microenvironment surrounding the lethal brain tumor glioblastoma multiforme decreased the cancer's growth and extended survival of laboratory mice with the cancer, scientists will report on Tuesday Dec. 17, at the American Society for Cell Biology (ASCB) annual meeting in New Orleans.

The rates of apoptosis, or programmed cell death, were higher in the mice treated with the experimental agent than in the untreated animals that also had high-grade glioblastomas, said Johanna Joyce, Ph.D., of the Memorial Sloan-Kettering Cancer Center (MSKCC) in New York City. As a result, the drug-treated laboratory mice survived many months longer than the untreated animals with the same cancer.

The experimental drug blocks cell receptors for colony-stimulating factor-1 (CSF-1R), which is essential to the differentiation and survival of tumor-associated macrophages and microglia (TAMS), which are the brain's front-line immune defense cells. The microenvironment that surrounds brain tumors contains many macrophages with this receptor.

Glioblastoma multiforme (GBM) is the most common and the most deadly adult primary brain tumor, with an average survival of just 14 months following diagnosis. Even with aggressive treatment by surgery, radiation and chemotherapy, most therapeutic approaches targeting the glioma cells in GBM fail.

Faced with this bleak picture, Dr. Joyce and colleagues MSKCC looked for an alternative strategy and turned to the cancer's cellular neighbors, the non-tumor cells that are part of the glioma microenvironment. In particular, they zeroed in on tumor-associated macrophages and TAMs.

When Dr. Joyce's lab used an inhibitor of the CSF-1 receptor (CSF-1R) to target TAMs in a mouse model of GBM, the treated mice survived many months longer than the control cohort. Their established, high-grade gliomas regressed in proliferation and malignancy, even though the glioma cells themselves were not the targets of the CSF-1R treatment.

With the TAMs blockaded by CSF-1 inhibitors, it was the tumor cells that showed increased rates of apoptosis. The TAMs were not even depleted in the treated mice, despite the drug blockade of their growth factor. Instead the TAMs survived by responding to growth factors secreted by the gliomas, including GM-CSF and IFN-γ, according to Dr. Joyce.

The MSKCC researchers also found that tumor spheres, freshly isolated from glioma patients in the surgery department at MSKCC, responded to the drug when implanted in animals. The CSF-1R blockade slowed intracranial growth in the patient-derived glioma xenografts.

Because GBM is the most common glioma, its genome was the first to be sequenced for the Cancer Genome Atlas, which parsed GBM into four genetic subtypes: proneural, neural, classical and mesenchymal. The mice used in Dr. Joyce's lab experiments model the proneural GBM subtype. All forms of GBM have a 2- to 3-person per 100,000 incidence rate in the U.S. and Europe, according to the National Brain Tumor Society. Because of its highly invasive phenotype, GBM is almost impossible to resect completely in surgery. Drug and radiation treatments are the standard follow-ups.

Dr. Joyce says that these new results, which were first reported only two months ago in Nature Medicine, http://www.ncbi.nlm.nih.gov/pubmed/24056773, are encouraging for planned clinical trials of CSF-1R inhibitors in combination with radiation therapy in glioma patients.

"We are optimistic that CSF-1R inhibitors may provide a more effective therapy than current treatments for the disease management of glioma patients," Dr. Joyce said.


'/>"/>

Contact: Cathy Yarbrough
cyarbrough@ascb.org
858-243-1814

John Fleischman
jfleischman@ascb.org

American Society for Cell Biology
Source:Eurekalert


Related biology news :

1. Pathogen study explores blocking effect of E. coli O157:H7 protein
2. Newly identified proteins make promising targets for blocking graft-vs.-host disease
3. Study suggests way to fight therapy resistant leukemia by blocking DNA repair
4. Blocking overactive receptor in Alzheimers recovers memory loss and more
5. Drug reduces fat by blocking blood vessels
6. Blocking DNA: HDAC inhibitor targets triple negative breast cancer
7. Study finds depletion of alveolar macrophages linked to bacterial super-infections
8. Practice Fusion Raises Additional $15M to Close Year of Exponential Platform Growth
9. High cholesterol fuels the growth and spread of breast cancer
10. Methylation signaling controls angiogenesis and cancer growth
11. Plant cell architecture: Growth toward a light source
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:3/23/2016)... 2016 Einzigartige ... und Stimmerkennung mit Passwörtern     ... MESG ), ein führender Anbieter digitaler Kommunikationsdienste, ... SpeechPro zusammenarbeitet, um erstmals dessen Biometrietechnologie einzusetzen. ... Möglichkeit angeboten, im Rahmen mobiler Apps neben ...
(Date:3/22/2016)... PROVO and SANDY, ... Screening Ontario (NSO), which operates the highest sample volume ... testing, and Tute Genomics and UNIConnect, leaders in clinical ... today announced the launch of a project to establish ... testing panel. NSO has been contracted ...
(Date:3/18/2016)... --> --> Competitive Landscape ... Vehicles, Physical infrastructure and Perimeter Surveillance & Detection Systems ... market and the continuing migration crisis in the ... has led visiongain to publish this unique report, which is ... & security companies in the border security market and ...
Breaking Biology News(10 mins):
(Date:6/27/2016)... , ... June 27, 2016 , ... ... for Amgen, will join the faculty of the University of North Carolina ... professor of strategy and entrepreneurship at UNC Kenan-Flagler, with a focus on the ...
(Date:6/24/2016)... ... ... While the majority of commercial spectrophotometers and fluorometers use the z-dimension of ... higher end machines that use the more unconventional z-dimension of 20mm. Z-dimension ... of the cuvette holder. , FireflySci has developed several Agilent flow cell product ...
(Date:6/23/2016)... TORONTO , June 23, 2016 /PRNewswire/ - ... Ontario biotechnology company, Propellon ... the development and commercialization of a portfolio of ... cancers. Epigenetic targets such as WDR5 represent an ... contribute significantly in precision medicine for cancer patients. ...
(Date:6/23/2016)... YORK , June, 23, 2016  The Biodesign ... to envision new ways to harness living systems and ... Modern Art (MoMA) in New York City ... than 130 participating students, showcased projects at MoMA,s Celeste ... Paola Antonelli , MoMA,s senior curator of architecture ...
Breaking Biology Technology: