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The CancerWeb Report, What's New In Cancer
Prostate Cancer: October 1995
Last modified on:
Tuesday, April 20, 1999 12:03:10
Copyright © 1994-2008, Information Ventures, Inc.
Prostate Cancer -
Within the past several years PSA (prostate-specific antigen) has
won for itself the role of the primary biochemical test for
prostate cancer formerly held by the less specific prostatic acid
phosphatase. However, little attention has been given to the
nature and role of this substance. PSA is a protease, an enzyme
that cleaves protein chains at the point where the amino acid
serine occurs, which is abundant in seminal fluid. Immediately
after ejaculation, seminal fluid coagulates, and then after some
20 minutes liquefies again due to hydrolysis of two high
molecular weight coagulative proteins by PSA; this probably
facilitates sperm migration. Is it possible that PSA can play a
similar role in a much more malevolent process? A paper
appearing in the October, 1995 issue of Clinical Cancer Research by a
group (Webber et al.) from Michigan State University suggests
that it can. A critical step in tumor invasion and metastasis is
the degradation of the proteins laminin, type IV collagen, and
fibronectin, which are responsible for holding together and
maintaining the basement membrane and extracellular matrix.
These tissue components would otherwise form a barrier
restricting tumor cell spread. These investigators showed that
PSA can degrade laminin and fibronectin. Furthermore, using a
reconstituted basement membrane Matrigel, they found that
blocking PSA activity with a PSA-specific monoclonal antibody
prevented invasion of the membrane by PSA-secreting human
prostate cancer cells LNCaP. If this finding is confirmed and
extended, PSA might eventually serve not only as an indicator of
prostate cancer, but equally importantly as a target for its
prevention and therapy. This would use compounds such as the
serpins, targeted to inhibit its invasion-facilitating serine
protease activity.
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