title: Tumor cell-expressed SerpinB2 is present on microparticles and inhibits metastasis.
abstract: 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.
authors.affiliation: Inflammation Biology Group, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, 4029, Australia.
authors.forename: Wayne A
authors.initials: WA
authors.lastname: Schroder
authors.forename: Lee D
authors.initials: LD
authors.lastname: Major
authors.forename: Thuy T
authors.initials: TT
authors.lastname: Le
authors.forename: Joy
authors.initials: J
authors.lastname: Gardner
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Sweet
authors.forename: Sabina
authors.initials: S
authors.lastname: Janciauskiene
authors.forename: Andreas
authors.initials: A
authors.lastname: Suhrbier
mesh_terms: D000818:Animals; D055252:Cell-Derived Microparticles; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008546:Melanoma, Experimental / Q000235:genetics* / Q000473:pathology; D051379:Mice; D009362:Neoplasm Metastasis / Q000235:genetics* / Q000473:pathology; D010718:Phosphatidylserines / Q000378:metabolism; D017396:Plasminogen Activator Inhibitor 2 / Q000096:biosynthesis* / Q000235:genetics; D011379:Prognosis; D011485:Protein Binding; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000378:metabolism
chemical_list: D010718:Phosphatidylserines; D017396:Plasminogen Activator Inhibitor 2; D014568:Urokinase-Type Plasminogen Activator
keywords: Annexin; SerpinB2; metastasis; microparticle; phosphatidylserine