Expression of SerpinB2 (
plasminogen activator inhibitor type 2/PAI-2) by certain
cancers is associated with a favorable prognosis. Although
tumor-associated host tissues can express SerpinB2, no significant differences in the growth of a panel of different
tumors in SerpinB2(-/-) and SerpinB2(+/+) mice were observed. SerpinB2 expression by
cancer cells (via lentiviral transduction) also had no significant effect on the growth of panel of mouse and human
tumor lines in vivo or in vitro. SerpinB2 expression by
cancer cells did, however, significantly reduce the number of
metastases in a B16
metastasis model. SerpinB2-expressing B16 cells also showed reduced migration and increased length of invadopodia-like structures, supporting the classical view that that
tumor-derived SerpinB2 is inhibiting extracellular
urokinase. Importantly, although SerpinB2 is usually poorly secreted, we found that SerpinB2 effectively reaches the extracellular milieu on the surface of 0.5-1 μm microparticles (MPs), where it was able to inhibit
urokinase. We also provide evidence that
annexins mediate the binding of SerpinB2 to
phosphatidylserine, a
lipid characteristically exposed on the surface of MPs. The presence of SerpinB2 on the surface of MPs provides a physiological mechanism whereby
cancer cell SerpinB2 can reach the extracellular milieu and access
urokinase plasminogen activator (uPA). This may then lead to inhibition of
metastasis and a favorable prognosis.