Urology & Kidney Disease News - Cleveland Clinic

22 Urology & Kidney Disease News
Prostate
Cell Surface Proteolytic Enzymes in Prostate Cancer
Qingyu Wu, MD, PhD
Proteolytic enzymes, also called proteases, function to split
other proteins in order to activate them, as in blood clotting,
or to degrade them, as in food digestion. Most
proteases are secreted soluble proteins. Recently, a new
class of trypsin-like proteases has been identified that is
anchored on the cell surface through an integral transmembrane
domain. These membrane proteases participate in a
variety of biological processes. We study two such proteases
that are involved in hypertension and prostate cancer.
Hepsin is a cell surface protease that shares a similar topological
structure with corin. (See page 39.) The hepsin gene
was first identified in the liver. Recent studies have shown
that hepsin plays an important role in prostate cancer. In
microarray analyses, hepsin is one of the most consistently
up-regulated genes in human prostate cancer. We found
that hepsin protein expression was highly elevated in
advanced prostate cancers and bone metastasis. In transgenic
mouse models, high levels of hepsin expression
promoted prostate cancer progression. Conversely, we
showed that anti-hepsin antibodies inhibited prostate
cancer cell invasion in culture. Elevated levels of hepsin
also are found in advanced renal, ovarian and breast cancers.
These data indicate that hepsin may contribute to
cancer invasion and progression. Currently, we are investigating
if hepsin can be used as a biomarker and therapeutic
target for the diagnosis and treatment of prostate cancer.
Key Point:
We are currently investigating if the protease hepsin, which
recently has been shown to play an important role in prostate
cancer, can be used as a biomarker and therapeutic
target for the diagnosis and treatment of prostate cancer.