Disease relevance of Serpinb5

• Recent studies of maspin in animal models strongly support maspin's role as an inhibitor against the growth of primary tumor sand the process of metastasis [1].
• This evidence strongly suggests that the induction of apoptosis in maspin-overexpressing cells represents a major mechanism by which maspin inhibits breast tumor progression [1].
• The maspin protein has tumor suppressor activity in breast and prostate cancers [2].
• These studies showed that maspin expression decreased tumor growth, reduced osteolysis, and decreased angiogenesis [3].
• Furthermore, the maspin-expressing tumors contained significant fibrosis and collagen staining, and exhibited a more glandular organization [3].

High impact information on Serpinb5

• Overexpression of maspin in breast tumor cells limits their growth and metastases in vivo [4].
• Maspin, a unique member of the serpin family, is a secreted protein encoded by a class II tumor suppressor gene whose downregulation is associated with the development of breast and prostate cancers [4].
• Maspin derivatives mutated in the serpin reactive site lost their ability to inhibit the migration of fibroblasts, keratinocytes, and breast cancer cells but were still able to block angiogenesis in vitro and in vivo [4].
• Blockade of the mannose receptor by intravenous administration of ovalbumin also prolonged the plasma half-life of 125I-t-PA to 3-4 min [5].
• Maspin expression inhibits osteolysis, tumor growth, and angiogenesis in a model of prostate cancer bone metastasis [3].

Chemical compound and disease context of Serpinb5

• PURPOSE: Maspin, a unique member of the serine protease inhibitor family, shows tumor suppressing activity for breast cancer progression and metastasis [6].
• Maspin expression profile in human prostate cancer (CaP) and in vitro induction of Maspin expression by androgen ablation [7].
• In contrast, exposure of hybrid B lymphomas to leupeptin, a protease inhibitor, induced a dose-dependent increase of CII-specific T cell response, while abrogating the I-Aq-restricted presentation of ovalbumin [8].
• OBJECTIVE AND DESIGN: We have evaluated the effects of the broad-spectrum cysteine protease inhibitor E64 on allergic lung inflammation in the mouse ovalbumin model of human asthma [9].

Biological context of Serpinb5

• In this report, we analyze the effect of maspin on tumor cell apoptosis under several stress conditions [1].
• Maspin plays an essential role in early embryonic development [10].
• Maspin (Mp) is a member of the serpin family with inhibitory functions against cell migration, metastasis and angiogenesis [10].
• Furthermore, we showed that maspin directly increased endodermal cell adhesion to laminin matrix but not to fibronectin [10].
• We conclude that deletion of maspin affects VE function by reducing cell proliferation and adhesion, thereby controlling early embryonic development [10].

Anatomical context of Serpinb5

• Such change results in an increased release of cytochrome c from mitochondria, thus the increased apoptosis in maspin-expressing cells [1].
• Data from embryoid body formation studies indicated that the Mp(-/-) EBs had a disorganized, endodermal cell mass and lacked a basement membrane layer [10].
• We showed that the embryonic ectoderm lineage was lost in the Mp(-/-) EBs, compared with that of the Mp(+/+) EBs [10].
• Maspin was specifically expressed in the visceral endoderm after implantation; deletion of maspin interfered with the formation of the endodermal cell layer, thereby disrupting the morphogenesis of the epiblast [10].
• In vitro, the ICM of the Mp(-/-) blastocysts failed to grow out appropriately [10].

Associations of Serpinb5 with chemical compounds

• Maspin is structurally a member of the serpin (serine protease inhibitors) superfamily but deviates somewhat from classical serpins [2].
• We show that treatment of Mp+/- mice with progesterone rescued the defect of ductal development [11].
• By using a functional assay, we show that a serum component other than beta 2-microglobulin enhances the presentation of ovalbumin peptides produced by cyanogen bromide cleavage [12].
• This earlier onset of S phase was not observed when Pronase treatment was performed in the presence of ovalbumin or the protease inhibitors phenylmethylsulfonyl fluoride or aprotinin [13].
• LNCaP cells cultured in androgen-depleted medium show induction of Maspin promoter activity in a promoter luciferase reporter assay [7].

Regulatory relationships of Serpinb5

• These complex interactions between maspin and sctPA in vitro suggest a mechanism by which maspin regulates plasminogen activation by sctPA bound to the epithelial cell surface [2].
• In addition, maspin promotes cell adhesion to the basement membrane and extracellular matrix components [14].

Other interactions of Serpinb5

• Tissue-type plasminogen activator is a target of the tumor suppressor gene maspin [2].
• However, targeted expression of maspin by the whey acidic protein gene promoter inhibits the development of lobular-alveolar structures during pregnancy and disrupts mammary gland differentiation [15].
• Maspin functions as tumor suppressor by increasing cell adhesion to extracellular matrix in prostate tumor cells [6].
• Immunohistochemistry analysis of maspin expression in the breast tissues of TGF-alpha transgenic mice showed a direct correlation between down-regulation of maspin expression and tumor progression [16].
• Those include serine protein inhibitor 2.2, maspin, mitogen- and stress-activated protein kinase 2, and macrophage colony-stimulating factor 1 [17].

Analytical, diagnostic and therapeutic context of Serpinb5

• To identify its role in embryonic development in vivo, we generated maspin knockout mice by gene targeting [10].
• METHODS: Maspin expression was analyzed by immunodot blot, Western blot, and RT-PCR analyses in cells obtained directly from human corneas in situ [18].
• The expression of mMaspin is down-regulated in tumor cells and is altered at different developmental stages of mammary gland. mMaspin has inhibitory properties similar to those of human maspin in cell culture, suggesting that the homologous proteins play similar physiological roles in vivo [19].
• When maspin was delivered locally to human prostate tumor cells in a xenograft mouse model, it blocked tumor growth and dramatically reduced the density of tumor-associated microvessels [4].
• Furthermore, vaccination with these recombinant poliovirus induced protective immunity against challenge with lethal doses of a malignant melanoma cell line expressing ovalbumin [20].

References