Interferon-inducible protein IFIXalpha inhibits cell invasion by upregulating the metastasis suppressor maspin

IFIXalpha, a member of the interferon-inducible HIN-200 family, has been identified as a putative tumor suppressor. However, the molecular mechanisms underlying IFIXalpha-mediated tumor suppression are poorly understood. In the present study, we demonstrated that the metastasis suppressor maspin acts as the downstream target of IFIXalpha. IFIXalpha suppressed the invasion activity of MDA-MB-468 breast cancer cells, and its inhibitory effect was reversed by the knockdown of maspin. Both Maspin mRNA and protein were upregulated by IFIXalpha. Histone deacetylase (HDAC) inhibitors, but not DNA methyltransferase inhibitor upregulated maspin, and HDAC1 inhibited the transactivation of maspin promoter. Although the HDAC1 protein was downregulated in IFIXalpha-expressing cells, IFIXalpha did not affect HDAC1 mRNA levels. Conversely, a proteasome inhibitor restored the level of HDAC1 protein in IFIXalpha-expressing cells, and the polyubiqutination of HDAC1 was promoted by IFIXalpha, suggesting that HDAC1 is regulated by IFIXalpha through a ubiquitin-proteasome pathway. Together, these data provide novel insights into the tumor-suppressive function of IFIXalpha.     

Decline in the expression of the serine proteinase inhibitor maspin is associated with tumour progression in ductal carcinomas of the breast

Maspin is an inhibitor of serine proteinases with tumour suppressor activity. Its expression appears to be reduced in advanced stages of breast cancer. A large series of archival breast tissue specimens has been examined, including normal glands (n=7), fibrocystic change (n=22), ductal carcinoma in situ (DCIS, n=12), infiltrating carcinomas (n=128) and their lymph node metastases (n=65), using a specific monoclonal antibody. Myoepithelium invariably showed strong maspin expression. In epithelial cells, the strongest expression was found in normal breast and fibrocystic change. A significant stepwise decrease in maspin expression (p<0.0001) occurred in the sequence DCIS - invasive cancer - lymph node metastasis. However, a subset of infiltrating carcinomas showed strong maspin expression, significantly associated with a lower rate of lymph node metastasis at the time of diagnosis (p<0.01). This was independent of tumour size and grade. The in vivo observations presented here are in keeping with data obtained in prior in vitro experiments. Maspin emerges as an indicator of tumour progression and metastatic potential, and might be exploited to predict breast cancer prognosis. According to in vitro data, its tumour suppressor activity is likely to involve both the modulation of cell motility/invasiveness and the inhibition of angiogenesis.     

Targeting maspin in endothelial cells to induce cell apoptosis

The diseases of cancer remain as some of the leading causes of death in the industrialised world, although there are a multitude of technologies being used in the field of medical oncology to combat these diseases and scientific research continues to make discoveries to improve patient outcomes. Some of this research has focused on the maspin gene and protein. Maspin is predicted to be a unique serpin with tumour suppressor activity. Recent studies have explored the use of maspin as a therapeutic agent against cancer. In one study, maspin was found to inhibit cancer growth and metastasis in a breast cancer mouse model through a maspin DNA-liposome therapy. A separate study showed the ability of maspin to induce apoptosis in tumour-specific endothelial cells. Taken together, these studies demonstrate the potential use of maspin as a viable anticancer therapeutic agent.     

Expression of maspin in colon cancers: its relationship with p53 expression and microvessel density

We studied the expression of maspin in colonic adenocarcinoma compared with adenoma and metastatic adenocarcinoma as well as the relationship with its possible regulator, p53. The colonic specimens consisted of 24 adenomas, 49 adenocarcinomas, and 17 metastatic adenocarcinomas. Immunohistochemical staining of paraffin sections was done with microwave-based antigen retrieval methods. The Ki-67 index and the microvessel density were counted using an image analysis system. Maspin expression was positive in 75.5% of adenocarcinomas and 91.7% of adenomas. Only 47.1% of the nodal metastasis showed positive maspin expression. In colonic adenocarcinomas, p53 expression was positive in 44.7% of the maspin-positive groups compared with 100% of the maspin-negative groups (P < 0.005). Colonic adenocarcinomas with the positive maspin expression groups showed less intense microvessel density (181.1 ± 54.2) than those of the negative maspin expression groups (256.1 ± 75.4, P < 0.001). In conclusion, we demonstrated maspin expression in colon cancer with a sequential decreased expression rate from adenoma to metastatic carcinomas, which signifies the tumor suppressive function of maspin, and an inverse correlation with p53 and microvesel density, which indicates the regulatory effect of p53 on maspin and anti-angiogenesis effect of maspin.     

Nuclear maspin detection in renal cell tumours: possible diagnostic role and correlation with p53 status

AIMS: To investigate the presence of maspin in renal tumours in an attempt to improve our understanding of the underlying mechanism of renal carcinogenesis and for diagnostic purposes. METHODS AND RESULTS: We examined 122 renal neoplasms of varying histological types and immunohistochemically investigated maspin and p53 expression. All clear cell carcinomas (CC) were negative for maspin, whereas oncocytomas (OC), papillary renal cell carcinomas (PC), chromophobe carcinomas (CPC) and, at least focally, collecting duct carcinomas (CDC) stained positively. We found that p53 positivity had a statistically significant correlation with metastasis (P=0.009) in CC and maspin showed a significant inverse correlation with the presence of metastasis in PC and CDC (P=0.02). CONCLUSIONS: The detection of maspin may be useful for differential diagnostic purposes and suggests a different underlying mechanism in the development of the various histological types of renal carcinomas.     

Maspin与EGFR在胃癌中的表达及临床意义

[目的]探讨Maspin与EGFR在胃癌组织中的表达及临床意义。[方法]采用免疫组化技术检测63例胃癌术后和20例正常胃组织的石蜡标本中Maspin与EGFR的表达水平,结合患者临床及病理特征进行相关性分析。[结果 ]Maspin、EGFR在胃癌组织中的阳性表达率分别为47.6%和84.1%,在对照组中为85.0%和0,两组之间有显著性差异(P<0.05)。Maspin、EGFR与肿瘤的浸润深度、淋巴结转移及临床分期相关(P<0.05),而与患者的性别、年龄、肿瘤大小、发生部位无关;另外,高中分化的胃癌组织中Maspin的阳性表达率(18/26)显著高于低分化组(69.2%vs.32.4%),而EGFR的表达与患者病理分化程度无明显关系。经Spearman等级相关检验分析,Maspin蛋白与EGFR的表达存在负相关。[结论]同时检测胃癌组织中Maspin与EGFR表达水平,对判断胃癌浸润转移潜能有一定参考价值。     

Maspin在乳腺癌组织中的表达及临床病理意义

目的探讨Maspin蛋白在乳腺癌中的表达及其意义。方法采用免疫组化Envision二步法检测82例浸润性乳腺癌、16例导管内癌、20例单纯性导管上皮增生及15例正常乳腺组织中Maspin蛋白的表达情况,并分析其临床病理意义。结果Maspin在正常乳腺组织、单纯性导管上皮增生、导管内癌及浸润性乳腺癌中表达率分别为100%、90%、75%、45.1%,呈逐级下降趋势,差异有显著意义（P〈0.05）。浸润性乳腺癌组织中Maspin蛋白表达与TNM分期及淋巴结转移呈负相关,并与患者的生存时间显著相关（P〈0.05）。结论Maspin蛋白的表达在乳腺癌的发生、演变过程中起重要作用。并与患者的生存期密切相关,可作为预测乳腺癌预后的参考指标。