Researchers identify enzyme involved in deadly brain tumors

January 17, 2013

One of the most common types of brain tumors in adults, glioblastoma multiforme, is one of the most devastating. Even with recent advances in surgery, radiation and chemotherapy, the aggressive and invasive tumors become resistant to treatment, and median survival of patients is only about 15 months. In a study published in Neuro-Oncology, researchers at Mayo Clinic identify an important association between the naturally occurring enzyme Kallikrein 6, also known as KLK6, and the malignant tumors.

"Our study of Kallikrein 6 showed that higher levels of this enzyme in the tumor are negatively associated with patient survival, and that the enzyme functions by promoting the survival of tumor cells," says senior author Isobel Scarisbrick, Ph.D., of Mayo Clinic's Department of Physical Medicine and Rehabilitation.

The findings introduce a new avenue for potential treatment of deadly glioblastomas: targeting the function of KLK6. The became more susceptible to treatment when researchers blocked the where the KLK6 enzyme can dock and initiate the survival signal.

Researchers looked at 60 samples of grade IV astrocytomas—also known at this stage as glioblastomas—as well as less aggressive grade III astrocytomas. They found the highest levels of KLK6 were present in the most severe grade IV tumors. Looking at the tumor samples, researchers found higher levels of KLK6 associated with shorter patient survival. Those with the highest levels lived 276 days, and those with lower levels lived 408 days.

"This suggests that the level of KLK6 in the tumor provides a prognosticator of patient survival," Dr. Scarisbrick says.

The group also investigated the mechanism of the enzyme to determine whether it plays a significant role in . Researchers also found glioblastoma cells treated in a with KLK6 become resistant to radiation and treatment.

"Our results show that KLK6 functions like a hormone, activating a signaling cascade within the cell that promotes tumor cell survival," Dr. Scarisbrick says. "The higher the level of the enzyme, the more resistant the tumors are to conventional therapies."

The study is the latest step in Dr. Scarisbrick's investigations of KLK6 in nervous system cells known as astrocytes. arise from astrocytes that have grown out of control. Her lab has shown that KLK6 also plays a role in the perseverance of inflammatory immune cells that occur in multiple sclerosis and in aberrant survival of T-lymphocyte leukemia cell lines.

"Our findings in glioma affirm KLK6 as part of a fundamental physiological mechanism that's relevant to multiple diseases and have important implications for understanding principles of tissue regeneration," she says. "Targeting KLK6 signaling may be a key to the development of treatments for pathologies in which it's necessary to intervene to regulate cell survival and tissue regeneration in a therapeutic fashion. Ultimately, we might be able to harness the power of KLK6 for the repair of damaged organs."

Explore further: Study shows halting an enzyme can slow multiple sclerosis in mice

Related Stories

Study shows halting an enzyme can slow multiple sclerosis in mice

April 30, 2012
Researchers studying multiple sclerosis(MS) have long been looking for the specific molecules in the body that cause lesions in myelin, the fatty, insulating cells that sheathe the nerves. Nearly a decade ago, a group at ...

Survival statistics show hard fight when malignant brain tumors appear at multiple sites

August 24, 2012
LOS ANGELES (Embargoed until 10 a.m. EDT on Aug. 24, 2012) – When aggressive, malignant tumors appear in more than one location in the brain, patient survival tends to be significantly shorter than when the disease starts ...

Study finds new targets for drugs to defeat aggressive brain tumor

December 14, 2012
University of Pittsburgh Cancer Institute (UPCI) researchers have identified over 125 genetic components in a chemotherapy-resistant, brain tumor-derived cell line, which could offer new hope for drug treatment to destroy ...

Minimizing side effects from chemoradiation could help brain cancer patients live longer

April 19, 2011
Minimizing neurological side effects in patients with high-grade glioma from chemoradiation may result in improved patient survival, a new study from radiation oncologists at the Kimmel Cancer Center at Jefferson suggests. ...

A culprit behind brain tumor resistance to therapy

March 5, 2012
Persistent protein expression may explain why tumors return after therapy in glioblastoma patients, according to a study published on March 5th in the Journal of Experimental Medicine.

Recommended for you

Physical activity could combat fatigue, cognitive decline in cancer survivors

July 25, 2017
A new study indicates that cancer patients and survivors have a ready weapon against fatigue and "chemo brain": a brisk walk.

Breaking the genetic resistance of lung cancer and melanoma

July 25, 2017
Researchers from Monash University and the Memorial Sloan Kettering Cancer Center (MSKCC, New York) have discovered why some cancers – particularly lung cancer and melanoma – are able to quickly develop deadly resistance ...

Anti-cancer chemotherapeutic agent inhibits glioblastoma growth and radiation resistance

July 24, 2017
Glioblastoma is a primary brain tumor with dismal survival rates, even after treatment with surgery, chemotherapy and radiation. A small subpopulation of tumor cells—glioma stem cells—is responsible for glioblastoma's ...

New therapeutic approach for difficult-to-treat subtype of ovarian cancer identified

July 24, 2017
A potential new therapeutic strategy for a difficult-to-treat form of ovarian cancer has been discovered by Wistar scientists. The findings were published online in Nature Cell Biology.

Immune cells the missing ingredient in new bladder cancer treatment

July 24, 2017
New research offers a possible explanation for why a new type of cancer treatment hasn't been working as expected against bladder cancer.

No dye: Cancer patients' gray hair darkened on immune drugs

July 21, 2017
Cancer patients' gray hair unexpectedly turned youthfully dark while taking novel drugs, and it has doctors scratching their heads.

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.