Enzyme helps drive aggressive prostate cancer


Enzyme helps drive aggressive prostate cancer


Researchers at the Mayo Clinic in Florida have discovered that an enzyme called PRSS3, or mesotrypsin, may help drive aggressive prostate cancer. Although they don't believe it is the only factor, they suggest it offers a new target for treatment, and have themselves developed a prototype compound that inhibits the enzyme's ability to promote the metastatic spread of the disease.

They write about their study, the first to link the enzyme to prostate cancer, in the 18 December online issue of the journal Molecular Cancer Research.

Enzyme May Help Free Cancer Cells from Surrouding Tissue

Senior investigator, Evette Radisky, a cancer biologist in the Mayo Clinic Cancer Center, explains in a press statement that PRSS3 is "a protease, which means it digests other molecules".

She says their findings suggest the enzyme promotes malignancy and invasiveness by changing the enviroment around prostate cancer cells, perhaps freeing them from surrounding tissue, but she adds:

"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."

Link Found By Searching Published Clinical Data

For their study, Radisky and colleagues searched publicly available data from clinical studies that had information on molecules that are "upregulated", that is switched on, in cancer.

PRSS3 has already been associated with breast, lung, and pancreatic cancer. In fact it was Radisky's team that discovered the link with breast cancer, but in this latest investigation they wanted to see if the enzyme was abnormally expressed in any other cancer, and at what stages.

Radisky says:

"The link between PRSS3 activity and aggressive prostate cancer jumped out at us."

She goes on to describe how their analysis revealed a "definitive trend of increasing PRSS3 expression with cancer progression".

PRSS3 Essential to Metastasis, But Also Possible to Switch Off

To confirm what they found in the data mining exercise, the team did some tests in lab mice bred to have human prostate cancer.

They found expression of PRSS3 was essential to prostate cancer metastasis. It did not spread in mice where PRSS3 was switched off.

When they crystallized and examined the enzyme's structure, they found a spot where they could insert a small drug molecule that disrupts the enzyme's ability to slice up other molecules.

"The protease has an active site that breaks down other proteins, and our inhibiting agent sticks to the site, shutting it down," explains Radisky.

Potential for Diagnosis and Treatment

The researchers see two ways forward from their discovery.

One is a diagnostic route: it may be possible to test prostate cancer patients for the presence of PRSS3, and that may help identify those at high risk for aggressive cancer.

The other is a treatment route: the prototype drug the team has developed could form the basis on "which to build an agent that can be used to treat these same patients," says Radisky.

"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," she adds.

In their paper, she and her colleagues conclude:

"This study defines mesotrypsin as an important mediator of prostate cancer progression and metastasis, and suggests that inhibition of mesotrypsin activity may provide a novel modality for prostate cancer treatment."

Funds from the Bankhead-Coley Florida Biomedical Research Program, the Department of Defense, and the National Cancer Institute helped finance the study.

In February 2012, a study reported online in the journal Cell, describes how an enzyme that reseals caps on damaged chromosomes, allows malignant prostate cancer cells to evade destruction and acquire more deadly characteristics.

And more recently, in August 2012, researchers at John Hopkins proposed a new kind of treatment for prostate cancer that finds and kills malignant cells while sparing healthy ones. The method, called theranostic imaging, targets and tracks potent drug therapies directly and only to cancer cells by binding an originally inactive form of drug chemotherapy, with an enzyme, to specific proteins on tumor cell surfaces.


Two Genes Together Drive Aggressive Prostate Cancer (Video Medical And Professional 2018).

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