Enzyme involved in deadly brain tumours identified

Researchers at Mayo Clinic have identified an important association between the naturally occurring enzyme Kallikrein 6, also known as KLK6 and glioblastoma multiforme, one of the most common types of brain tumours in adults.

"Our study of Kallikrein 6 showed that higher levels of this enzyme in the tumour are negatively associated with patient survival, and that the enzyme functions by promoting the survival of tumour cells," said senior author Isobel Scarisbrick, 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 tumour 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 tumours. Looking at the tumour 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 tumour provides a prognosticator of patient survival," Scarisbrick said in a statement.

The group also investigated the mechanism of the enzyme to determine whether it plays a significant role in tumour 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 signalling cascade within the cell that promotes tumour cell survival," Scarisbrick said.

"The higher the level of the enzyme, the more resistant the tumours are to conventional therapies," Scarisbrick said.

The study was published in the journal Neuro-Oncology.