Identification of a novel target for glioblastoma treatment

June 18, 2012
Identification of a novel target for glioblastoma treatment

(Medical Xpress) -- A recent study from scientists at the Friedrich Miescher Institute for Biomedical Research has identified a novel target for the treatment of malignant brain tumors. The scientists found that the Mer receptor tyrosine kinase (MerTK) is highly expressed in human brain tumors but absent from normal adult brain tissue. MerTK not only increases the invasive potential of brain tumor-derived cells but also promotes their survival when treated with chemotherapeutics. Conversely, the authors demonstrate that loss of MerTK strongly reduces the invasive capacity of tumor cells, making it an attractive target for future brain tumor therapies.

Glioblastoma multiforme (GBM) is the most common and aggressive brain tumor in adults. GBM tumor cells multiply at high rates and readily invade adjacent healthy . The mean survival of a patient diagnosed with GBM amounts to 14 months, also reflecting the high incidence of resistance against standard therapies. Alarmingly, radio- and chemotherapies, routinely used to treat GBM patients after surgical removal of the primary tumor, have been reported to increase the aggressiveness of residual tumor cells resulting in the recurrence of secondary .

In search of alternative therapeutic approaches, scientists from the group of Brian Hemmings at the Friedrich Miescher Institute for Biomedical Research teamed up with clinicians and pathologists. They profiled human GBM tumors to define common molecular signatures with the ultimate goal to specifically target the tumor cells while sparing their healthy neighbors. In this context, Yuhua Wang, a collaborator in Hemmings laboratory, and her colleagues have discovered that MerTK is strongly expressed in malignant gliomas but absent from normal brain. To study the underlying mechanism, they turned to established GBM-derived cell lines and found that MerTK is not expressed in these cells. However, when they analyzed GBM-derived spheres – cell aggregates that are grown in serum-free medium and thus resemble the actual tumor situation more closely – they found high MerTK levels. Subsequently, Wang established that MerTK was essential to maintain the rounded morphology and invasive capacity of GBM cells. All effects were reversed when a mutant form of MerTK was used that could no longer undergo phosphorylation at three critical residues. Further experiments revealed that MerTK drives GBM cell invasion by regulating actomyosin contractility, thus helping the invading cell to “squeeze through” small spaces into the surrounding brain tissue. Lastly, the scientists discovered that MerTK protein expression was induced by DNA damage and protected glioma cells against cytotoxic insults. This last finding suggests that MerTK is – at least in part –responsible for glioma cell survival and enhanced invasion after radiotherapy.

“Radiotherapy is the most commonly used therapeutic modality for malignant gliomas; it significantly prolongs the patients’ life expectancy”, explains Wang. “But although many gliomas initially respond, all of them invariably recur, even in combination with surgery and chemotherapy, a phenomenon we still don’t fully understand. MerTK, which is overexpressed in 90% of the analyzed GBM tumors, appears to support characteristics that are vital for , namely resistance against DNA-damaging agents and invasion. We therefore propose MerTK as a potential new target for the treatment of .”

Explore further: A thought-provoking new therapeutic target for brain cancer?

More information: Wang Y, et al. (2012). Mer receptor tyrosine kinase promotes invasion and survival in glioblastoma multiforme. Oncogene [Epub ahead of print]

Related Stories

A thought-provoking new therapeutic target for brain cancer?

February 1, 2012
Glioblastoma multiforme (GBM) is the most common of all malignant brain tumors that originate in the brain. Patients with GBM have a poor prognosis because it is a highly aggressive form of cancer that is commonly resistant ...

How brain tumors invade

December 12, 2011
Scientists have pinpointed a protein that allows brains tumors to invade healthy brain tissue, according to work published this week in the Journal of Experimental Medicine.

Glioblastoma multiforme in the Dock

November 14, 2011
Glioblastoma multiforme (GBM) is the most common malignant brain cancer in humans. Patients with GBM have a poor prognosis because it is a highly aggressive form of cancer that is commonly resistant to current therapies. ...

Recommended for you

New study reveals breast cancer cells recycle their own ammonia waste as fuel

October 19, 2017
Breast cancer cells recycle ammonia, a waste byproduct of cell metabolism, and use it as a source of nitrogen to fuel tumor growth, report scientists from Harvard Medical School in the journal Science.

US regulators approve 2nd gene therapy for blood cancer

October 19, 2017
U.S. regulators on Wednesday approved a second gene therapy for a blood cancer, a one-time, custom-made treatment for aggressive lymphoma in adults.

New findings explain how UV rays trigger skin cancer

October 18, 2017
Melanoma, a cancer of skin pigment cells called melanocytes, will strike an estimated 87,110 people in the U.S. in 2017, according to the Centers for Disease Control and Prevention. A fraction of those melanomas come from ...

Drug yields high response rates for lung cancer patients with harsh mutation

October 18, 2017
A targeted therapy resurrected by the Moon Shots Program at The University of Texas MD Anderson Cancer Center has produced unprecedented response rates among patients with metastatic non-small cell lung cancer that carries ...

Possible new immune therapy target in lung cancer

October 18, 2017
A study from Bern University Hospital in collaboration with the University of Bern shows that so-called perivascular-like cells from lung tumors behave abnormally. They not only inadequately support vascular structures, but ...

Many pelvic tumors in women may have common origin—fallopian tubes

October 17, 2017
Most—and possibly all—ovarian cancers start, not in ovaries, but instead in the fallopian tubes attached to them.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.