Role of maspin in cancer

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.

Culture phases, cytotoxicity and protein expressions of agarose hydrogel induced Sp2/0, A549, MCF-7 cell line 3D cultures

“…These unnatural geometric constraints make the cells behave in a different way from cells seen in their natural environment (Berardi et al 2013). With the introduction of a matrix into the culture conditions, cells are observed to adopt a phenotype comparable to their in vivo conditions.…”

“…This results from the formation of aggregates or cell masses that are induced by the matrix. Thus, in 3D cultures, the adhesion proteins are seen all over the surface implying that the cells interact with the matrix analogous to their behaviour in vivo (Berardi et al 2013). Fig.…”

“…The cells in 3D cultures exhibit slower progression when compared to their 2D counterparts (Figure 3, panel B) Maspin has been found to be down-regulated in certain cancer types (breast, gastric and prostrate) while being up-regulated in others (pancreatic, thyroid and colorectal). This suggests that the role of maspin differs from one tissue type to another one (Berardi et al 2013). 3D cultures prove advantageous to study such proteins because cells in 2D cultures do not expand, differentiate and function according to their cell types.…”

Maspin Expression and its Metastasis Suppressing Function in Prostate Cancer

“…In normal breast and prostate epithelial cells, maspin is highly expressed and found to be localized mostly in the cytoplasm but has also been detected in the nucleus, secretory vesicles, and occasionally at the cell surface [6][7][8]. Maspin expression is almost completely suppressed in the human prostate cancer LNCaP, DU145, and PC-3 cell lines [9].…”

“…Although maspin might lack the ability to inhibit serine proteases, its biological function can be attributed to RCL, which can be derived from its crystal structure [6]. Recent studies of maspin have provided evidence for its ability to regulate cell adhesion, motility, apoptosis, and angiogenesis, which has been of utmost interest in medical field attempting to use maspin as a method of therapeutic intervention for prostate cancer and other forms of malignancies [3][4][5][6][7].…”