Enzyme Identified in Deadly Brain Tumors

An important association has been found between the naturally occurring enzyme Kallikrein 6, also known as KLK6, and malignant tumors.

The clinical value of KLK6 as a prognostic indicator of glioblastoma multiforme (GBM) patient survival and its activity in promoting resistance to cytotoxic agents has been investigated.

Scientists at the Mayo Clinic (Rochester, MN, USA) examined the relationship between KLK6 and patient survival in 60 primary GBM tumor specimens and delineated the significance of elevated KLK6 to tumor cell survival. Tissue microarrays were prepared from tumor core samples obtained from surgically resected formalin-fixed paraffin-embedded primary glioma specimens. Real-time reverse transcription (RT)-PCR was used to determine KLK6 ribonucleic acid (RNA) expression levels in GBM patient and cell line samples.

The 60 samples were either from grade IV astrocytomas, also known at this stage as glioblastomas, or from less aggressive grade III astrocytomas. The investigators found the highest levels of KLK6 were present in the most severe grade IV tumors. The scientists found higher levels of KLK6 associated with shorter patient survival, as those with the highest levels lived 276 days, and those with lower levels lived 408 days. KLK6 immunostaining was detectable in all tumor cores examined, with the level of immunoreactivity was markedly elevated in grade IV tumors at 7.7 ± 2.4 compared to grade III specimens at 2.4 ± 1.5.

Isobel A. Scarisbrick, PhD., the senior author said, "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. This suggests that the level of KLK6 in the tumor provides a prognosticator of patient survival." Glioblastoma multiforme is one of the most common types of brain tumors in adults, and 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. The study was published January 10, 2013, in the journal Neuro-Oncology.

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