Maspin (mammary serine protease inhibitor) also known as serpin B5 is a protein that in humans is encoded by the SERPINB5gene. This protein belongs to the serpin (serine protease inhibitor) superfamily.SERPINB5 also functions as a tumor suppressor gene in epithelial cells. The expressed protein suppresses the ability of cancer cells to invade and metastasize other tissues. The protein also functions as an angiogenesis inhibitor.
Maspin is a member of the serpin superfamily of serine protease inhibitors. The primary function of most members of this family is to regulate the breakdown of proteins by inhibiting the catalytic activity of proteinases. Through this mechanism of action, serpins regulate a number of cellular processes including phagocytosis, coagulation, and fibrinolysis.
Serpins have a complex structure, a key component of which is the reactive site loop, RSL. Inhibitory serpins transition between a stress and relaxed stage. The catalytic serine residue in the protease target attacks the stressed conformation of the RSL loop to form an acyl intermediate. The loop then undergoes a conformational change to the relaxed state irreversibly trapping the protease in an inactive state. Hence the serpine functions as a suicide inhibitor of the protease. This transition does not occur in serpins that lack inhibitory activity.
Though maspin is a part of the serpin superfamily, its mechanism of action differs somewhat from other members of the family. More specifically, the RSL loop in maspin does not transition between a stressed and relaxed state and is shorter than the RSL loop in other serpins. However this shorter loop is necessary for maspin’s ability to suppress tumors by inhibiting cell invasion and motility. Furthermore, while maspin is an inhibitory serpin, but does not inhibit serine proteinases. Instead, maspin functions as an inhibitor of histone deacetylase 1 (HDAC1).
Tumors require blood in order to proliferate. Tumors invade other cells and begin to spread through a process known as metastasis. Metastasis is one of the key steps in cancer progression that causes cancer-related deaths. Maspin has been shown to inhibit all of these functions. Maspin was able to inhibit the invasion of breast cancer. Normal mRNA expresses maspin, but tumor-derived mammary epithelial cells do not. The consistent down regulation of maspin in breast cancer suggests maspin place a role in tumor suppression. Maspin significantly correlates with tumor differentiation grade or lymph node status, but not with recurrence rates. Maspin reduced the motility of tumor cells by 75 percent within 24 hours.
Maspin treatment of breast cancer cells leads to increased focal adhesions and stress fibers that in turn reduce cell motility. Less motile breast cancer cells were able to “revert to a more epithelial-like phenotype”. When tumor cells are treated with maspin, 53 percent of the tumors stopped growing completely with in a week. Tumor growth returned once the addition of maspin ceased. In addition, maspin able to regulate motility.
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