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 tumor cells became more susceptible to treatment when researchers blocked the receptors 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 tumor growth. Researchers also found glioblastoma cells treated in a petri dish with KLK6 become resistant to radiation and chemotherapy 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. Glioblastomas 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 is 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."The study was funded by a National Institutes of Health Brain Tumor SPORE grant, an NIH Mayo Neuro-oncology Training Grant and a grant from the National Institute of Neurological Diseases and Stroke. Other authors include Kristen Drucker, Ph.D., Alex Paulsen, Caterina Giannini, M.D., Ph.D., Paul Decker, Joon Uhm, M.D., Brian O'Neill, M.D., and Robert Jenkins, M.D., Ph.D., all of Mayo Clinic; and Sachiko Blaber and Michael Blaber, Ph.D., of Florida State University.
Journalists can become a member of the Mayo Clinic News Network for the latest health, science and research news and access to video, audio, text and graphic elements that can be downloaded or embedded.
Bryan Anderson | EurekAlert!
Modern genetic sequencing tools give clearer picture of how corals are related
17.08.2017 | University of Washington
The irresistible fragrance of dying vinegar flies
16.08.2017 | Max-Planck-Institut für chemische Ökologie
Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.
As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...
Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.
Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...
For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.
While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...
An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.
The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...
A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.
Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...
16.08.2017 | Event News
04.08.2017 | Event News
26.07.2017 | Event News
17.08.2017 | Physics and Astronomy
17.08.2017 | Earth Sciences
17.08.2017 | Physics and Astronomy