An enzyme, known as PRSS3, is specifically associated with aggressive prostate cancer risk, researchers from the Mayo Clinic, Florida reported this week in the journal Molecular Cancer Research.
The scientists, who claim they are the first to link the enzyme to prostate cancer, added that they have developed a compound that can stop PRSS3 from encouraging metastasis – when cancer spreads beyond its point of origin to other parts of the body.
Senior investigator, Evette Radisky, Ph.D., a cancer biologist, said:
“This molecule is a protease, which means it digests other molecules. Our data suggests PRSS3 activity changes the environment around prostate cancer cells – perhaps by freeing them from surrounding tissue – to promote malignancy and invasiveness.
I don’t think PRSS3 is the only factor involved in driving aggressive prostate cancer, but it may be significant for a certain subset of this cancer – the kind that is potentially lethal.”
Dr. Radisky and team had set out to determine, from data on previous clinical trials which had information on molecules that are irregularly switched on in cancer, which enzymes encouraged metastasis.
In a previous study they had identified a link between the protease and the initial stages of breast cancer.
They wanted to find out whether any other cancer abnormally expresses this protease, and when. They gathered and analyzed data from several sources.
A protease is an enzyme that breaks down proteins and peptides.
Dr. Radisky said:
“The link between PRSS3 activity and aggressive prostate cancer jumped out at us. We found a definitive trend of increasing PRSS3 expression with cancer progression.”
In an animal experiment using mice with prostate cancer, they showed that protease expression was vital for prostate cancer metastasis. When PRSS3 was silenced, the cancer did not spread.
The team had previously crystallized the structure of the PRSS3 protease, and identified a place on the enzyme where a small protein therapeutic could bind to plug up the “scissoring” action of the molecule.
Dr Radisky said “The protease has an active site that breaks down other proteins, and our inhibiting agent sticks to the site, shutting it down.”
The authors believe their breakthrough could pave the way for “several possible future clinical applications”.
Prostate cancer patients could be tested for the presence of the enzyme, so that doctors could identify which ones had the highest risk of metastasis, Dr Radisky added.
The team have developed a “prototype drug”, which they say provides a template upon which an agent could be used to treat patients with aggressive prostate cancer. Dr. Radisky said:
“Our inhibitor does not have the characteristics we need for a clinically useful drug. But it puts us on the right path to develop one.”
Written by Christian Nordqvist