Abstract
Maspin (mammary serine protease inhibitor), is a member of the serine protease inhibitor/non-inhibitor superfamily. Its expression is down-regulated in breast, prostate, gastric and melanoma cancers but over-expressed in pancreatic, gallbladder, colorectal, and thyroid cancers suggesting that maspin may play different activities in different cell types. However, maspin expression seems to be correlated with better prognosis in prostate, bladder, lung, gastric, colorectal, head and neck, thyroid and melanoma cancer. In breast and ovarian cancer maspin significance is associated with its subcellular localization: nucleus maspin expression correlates with a good prognosis, whilst in pancreatic cancer it predicts a poor prognosis. Since tumor metastasis requires the detachment and invasion of tumor cells through the basement membrane and stroma, a selectively increased adhesion by the presence of maspin may contribute to the inhibition of tumor metastasis. Furthermore the different position of maspin inside the cell or its epigenetic modifications may explain the different behavior of the expression of maspin between tumors. The expression of maspin might be useful as a prognostic and possibly predictive factor for patients with particular types of cancer and data can guide physicians in selecting therapy. Its expression in circulating tumor cells especially in breast cancer, could be also useful in clinical practice along with other factors, such as age, comorbidities, blood examinations in order to select the best therapy to be carried out. Focusing on the malignancies in which maspin showed a positive prognostic value, therapeutic approaches studied so far aimed to re-activate a dormant tumor suppressor gene by designed transcription factors, to hit the system that inhibits the expression of maspin, to identify natural substances that can determine the activation and the expression of maspin or possible “molecules binds” to introduce maspin in cancer cell and gene therapy capable of up-regulating the maspin in an attempt to reduce primarily the risk of metastasis.Further studies in these directions are necessary to better define the therapeutic implication of maspin.
Highlights
Maspin, is a member of the serine protease inhibitor/non-inhibitor superfamily, like plasminogen activator inhibitors 1 and 2 and α1-antitrypsin
In 134 bladder cancer patients, the relationship between clinico-pathological features and Maspin was examined and a high Maspin expression was found in low grade and advanced stage. These results indicated that Maspin expression might predict a better prognosis for bladder carcinoma and it could play a role in tumor progression [84]
It is important to continue to search for the maspin in different tumor types in order to better define its prognostic significance, to refine the definition techniques of cellular compartmentalization and to evaluate the possible therapeutic implications considering peculiarities of expression of maspin in various cancers (Table 10)
Summary
Maspin (mammary serine protease inhibitor), is a member of the serine protease inhibitor/non-inhibitor superfamily (serpin), like plasminogen activator inhibitors 1 and 2 and α1-antitrypsin. Specimens from 162 nonmuscle invasive bladder cancer patients treated by transurethral resection were examined They showed that a low maspin protein expression was correlated with a higher incidence of tumor progression and emphasized a possible clinical role of this novel tumor suppressor gene in transitional cell carcinoma of the bladder [81]. In another recent study on 156 colorectal cases, significant correlations between cytoplasmic expression and high tumor grade and between nuclear expression, high tumor budding and worse OS, were shown These findings suggest a compartment-dependent function of maspin in colorectal cancer, which can be useful in identifying stage II cases with a higher risk for fatal outcome with a possible benefit from adjuvant chemotherapy [110]. Resveratrol inhibits cell proliferation, induces apoptosis of human prostate carcinoma and acute lymphoblastic leukemia cells and increases maspin levels through Akt pathway [159,160,161,162,163]
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