Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Blocking tumor-associated macrophages decreased glioblastoma's growth & extended survival in mice

16.12.2013
Rates of programmed cell death higher in mice treated with experimental drug than in untreated animals with same cancer

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-ã, 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:

Johanna Joyce, Ph.D.
Memorial Sloan-Kettering Cancer Center
New York, NY
646-888-2048
JoyceJ@mskcc.org
ASCB PRESS CONTACTS:
John Fleischman
jfleischman@ascb.org
513-706-0212
Cathy Yarbrough
Cyarbrough@ascb.org
858-243-1814
Author will present, "CSF-1R inhibition alters macrophage polarization and blocks glioma progression," Tuesday, Dec. 17, during the 3:50 to 4:10 p.m. mini-symposium titled, "Tumor Microenvironment as a Driver and Target in Cancer Progression."

Cathy Yarbrough | EurekAlert!
Further information:
http://www.ascb.org

More articles from Life Sciences:

nachricht Flow of cerebrospinal fluid regulates neural stem cell division
22.05.2018 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Chemists at FAU successfully demonstrate imine hydrogenation with inexpensive main group metal
22.05.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

Im Focus: Entangled atoms shine in unison

A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.

The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...

Im Focus: Computer-Designed Customized Regenerative Heart Valves

Cardiovascular tissue engineering aims to treat heart disease with prostheses that grow and regenerate. Now, researchers from the University of Zurich, the Technical University Eindhoven and the Charité Berlin have successfully implanted regenerative heart valves, designed with the aid of computer simulations, into sheep for the first time.

Producing living tissue or organs based on human cells is one of the main research fields in regenerative medicine. Tissue engineering, which involves growing...

Im Focus: Light-induced superconductivity under high pressure

A team of scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg investigated optically-induced superconductivity in the alkali-doped fulleride K3C60under high external pressures. This study allowed, on one hand, to uniquely assess the nature of the transient state as a superconducting phase. In addition, it unveiled the possibility to induce superconductivity in K3C60 at temperatures far above the -170 degrees Celsius hypothesized previously, and rather all the way to room temperature. The paper by Cantaluppi et al has been published in Nature Physics.

Unlike ordinary metals, superconductors have the unique capability of transporting electrical currents without any loss. Nowadays, their technological...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

Supersonic waves may help electronics beat the heat

18.05.2018 | Power and Electrical Engineering

Keeping a Close Eye on Ice Loss

18.05.2018 | Information Technology

CrowdWater: An App for Flood Research

18.05.2018 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>