ABSTRACT
Serine protease inhibitors (serpins) are comprised of a large family of molecules that play a variety of physiological roles in vivo. 1-3 Not all molecules that inhibit serine proteases are termed serpins. But all serpins have a very special protein structure and molecular weight about 400 amino acids. 2 Serpins exist in almost every organism, from virus to mammals. 3' 5 They can be divided into two categories: inhibitory and non-inhibitory serpins. Non-inhibitory serpins, typified by ovalbumin and PEDF, do not exhibit protease inhibitor activity, but rather function as a storage protein and neural differentiation factor, respectively.6,7 Inhibitory serpins ablate serine proteases through their functional domain-reactive site loop (RSL) . 2 Interestingly, some inhibitory serpins have evolved other regulatory functions. For example, plasminogen activator inhibitor 1 (PAI-1 ) not only specifically inhibits tPA and uPA,8,9but also regulates cell adhesion, which is independent of its protease inhibitor function, by blocking integrin a v (33 binding to vitronectin. 10 ,1 1 This implies that serpins not only play diverse roles as a class, but also a single serpin molecule may possess multiple functions. 12
Maspin is a unique member of the serpin family that shares extensive homology with monocyte-neutrophil elastase inhibitor, 3 PAI-2 and other serpins. 13 ,14 Initially identified as a class II tumor suppressor gene, maspin has been shown to inhibit invasion and motility of mammary tumors. 13 ,15 ,16 Tumor transfectants expressing maspin exhibit decreased growth and metastasis in nude mice. 13 Maspin gene expression is not detected in most breast tumors and loss of its expression is correlated with tumor invasiveness. 17 Maspin is also found to be a potent angiogenesis inhibitor. 18 In human breast tissue, maspin seems to be present more in luminal than myoepithelial cells, and it has been suggested that those maspin-expressing myoepithelial cells form a defensive barrier for the progression from ductal carcinoma in situ to more invasive carcinomas. 19 A dispute exists regarding whether maspin acts as a protease inhibitor among biochemists.2 0 '22 Evidence from my laboratory indicates that maspin, regardless of whether it inhibits protease or not, possesses other functions independent of anti protease action(Zhang et al, unpublished data) . 16
M aspin , edited by Mary J.C. Hendrix. © 2 0 0 2 Eurekah.com
In this Chapter I intend to summarize the studies on maspin done by my group in the last few years and some works that are done by others but are closely related to ours. They will be divided into three sections: 1 ) maspin gene expression; 2 ) role of maspin in normal mouse development and 3 ) role of maspin in tumor progression and angiogenesis.
