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Biotech / Medical : Cistron Biotechnology(CIST)$.30
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To: scaram(o)uche who wrote (701)6/13/1997 2:15:00 PM
From: Rudy Saucillo   of 2742
 
Here's the last abstract for today - another study evaluating the anti-metastasis properties of PAI-2. This one is out of Scripps Research Institute.

Rudy

Overexpression of plasminogen activator inhibitor 2 in human
melanoma cells inhibits spontaneous metastasis in scid/scid mice.

Mueller BM, Yu YB, Laug WE
Department of Immunology, Scripps Research Institute, La Jolla,
CA 92037.

Proc Natl Acad Sci U S A 1995 Jan 3;92(1):205-9

A metastatic human melanoma cell line that produces
urokinase-type plasminogen activator was stably transfected with
cDNA encoding human plasminogen activator inhibitor 2 (PAI-2).
Transfected clones expressed PAI-2 at levels two to nine times
higher than both the parental cell line and mock transfectants,
as detected by ELISA of cell lysates and conditioned medium. The
clone with the highest PAI-2 expression exhibited complete
inhibition of soluble and cell-surface-bound plasminogen
activator activity. The level of PAI-2 overexpression in these
clonal cell lines correlated positively with the inhibition of
their ability to degrade extracellular matrix in vitro. Parental,
mock-transfected, and PAI-2-transfected cell lines produced
rapidly growing tumors when injected s.c. into the skin of mice
with severe combined immunodeficiency. The tumors producing the
highest levels of PAI-2 were surrounded by a dense tumor capsule.
Both parental cells and mock-transfected cells invariably
metastasized from s.c. tumors to lymph nodes and lungs of mice.
PAI-2-transfected cell lines produced significantly less or no
metastases. Taken together, these data indicate a critical role
for plasminogen activator activity in melanoma invasion and
metastasis.
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