Maspin, a member of the
serpin family of
serine protease inhibitors, was originally identified as a
tumor suppressor that is expressed in normal mammary epithelial cells but is reduced or absent in
breast carcinomas. Early enthusiasm for
maspin as a
biomarker for
disease progression has been tempered by clinical data that associates
maspin with favourable outcomes in some studies and poor prognosis in others. Here, we review all of the published clinical studies for
maspin in breast and
ovarian cancers and propose that the apparent discordance between clinical reports is a consequence of differential cellular distribution of
maspin. Indeed, it was thought that an extracellular pool of
maspin possessed
tumor suppressor activity, acting by inhibiting migration and increasing cell adhesion. Recent evidence from our group and others indicates, however, that the nuclear localization of
maspin in
cancer cells is necessary for its
tumor suppressor activity. We provide additional data here to demonstrate that nuclear-localized
maspin binds to
chromatin and is required to effectively prevent cells from metastasizing. Our knowledge of other
serpins that localize to the nucleus should help to inform future studies of nuclear
maspin. Elucidation of the molecular mechanisms regulating the localization and activities of
maspin should pave the way for the development of improved diagnostics and
therapies for
cancer.