Serpins for Diagnosis and Therapy in Cancer
Donghang Zheng, Hao Chen, Jennifer Davids, Marsha Bryant and Alexandra Lucas
Affiliation: Ethel Smith Chair Vasculitis Research, Section Head Vascular Research, Professor of Medicine, Divisions of Cardiovascular Medicine and Rheumatology, University of Florida, 1600 SW Archer Rd, PO BOX 100277, Gainesville, FL, USA.
Keywords: Cancer, Maspin, neuroserpin, PAI-1, PEDF, Serp-1, serpin.
Serine protease inhibitors (Serpins) play an important role in regulating a wide array of diverse biological
activities, representing up to 2-10% of circulating plasma proteins. The serpin suicide inhibitors regulate coagulation
(thrombosis and thrombolysis), neurotrophic factors, hormone transport, complement and inflammation, angiogenesis,
hormone transport, and blood pressure among many other biological reactions. Select serpins have been associated with
progression or remission of selected cancers, making them valuable for therapeutic or diagnostic use. Plasminogen
activator inhibitor-1 (PAI-1), the main regulator of thrombolysis, has the potential to either reduce or accelerate tumor
growth but blockade of PAI-1 has recently been reported to reduce cancer cell migration, proliferation and survival
through modulating the function of urokinase-type plasminogen activator receptor. Maspin is a non-inhibitory serpin, that
increases cancer cell sensitivity to apoptosis and inhibits cancer cell migration thus providing a serpin that blocks tumor
gorwth. Pigment epithelium derived factor (PEDF) has potent anti-angiogenesis activity and also promotes cancer cell apoptosis.
Among other serpins, the mammalian serpin, neuroserpin, and the myxomavirus derived serpin, Serp-1 are under
investigation in our lab for their potential tumor-suppressive functions. Further study on the efficacy and mechanisms of
serpin mediated anti-cancer activity is warranted in order to develop new serpin-based approaches in cancer therapy.
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