Poster Presentation 6th Australian Health and Medical Research Congress 2012

SerpinB2 is present on microparticles and inhibits tumour metastasis (#455)

Wayne A Schroder 1 , Lee D Major 1 , Thuy T Le 1 , Joy Gardner 1 , Andreas Suhrbier 1
  1. Queensland Institute of Medical Research, Herston, Qld, Australia

The physiological role of SerpinB2 (also known as plasminogen activator inhibitor type 2; PAI-2) remains unclear, although recent evidence suggests SerpinB2 modulates the adaptive immune response, with dysregulated expression and polymorphisms associated with a range of inflammatory diseases including pre-eclampsia, lupus, asthma, scleroderma and periodontitis (1). In addition, SerpinB2 expression by certain cancers, particularly breast cancer, is associated with a favourable prognosis. Using mouse models to understand the latter phenomena, we show that neither host nor tumour SerpinB2 expression had any significant effect on tumour growth. However, tumour (but not host) expression of SerpinB2 significantly reduced metastasis. SerpinB2 expressing tumour cells showed reduced migration and decreased invadopodia length in vitro, suggesting SerpinB2-mediated inhibition of urokinase plasminogen inhibitor (uPA). Although SerpinB2 inhibits uPA in vitro, if, when and how this occurs in vivo remains unresolved (1). SerpinB2 emerged to be present on the surface of 0.5-1 ┬ÁM microparticles (MPs) produced by multiple tumour cell lines, consistent with published data showing SerpinB2 expression in synciototrophoblast-derived MPs. We showed that SerpinB2 association with MPs was mediated by annexins, and that MP-associated SerpinB2 was able to form covalent complexes with uPA. These data for the first time provide a physiological mechanism whereby SerpinB2 can access the extracellular compartment to inhibit uPA. In addition, the association of SerpinB2 with MPs provides a critical insight into the role of SerpinB2 in cancer and inflammatory conditions.

(1). Schroder WA, Major L, Suhrbier A (2011). The role of SerpinB2 in immunity. Crit Rev Immunol 31: 15-30.