VEGF and EMMPRIN expression correlates with survival of patients with osteosarcoma

Aim

To investigate the clinicopathologic characteristics of Vascular Endothelial Growth Factor (VEGF) and Extracellular Matrix Metalloproteinase Inducer (EMMPRIN) expression in osteosarcoma, and to evaluate the clinical significance of these two markers in the survival of osteosarcoma.

Methods

VEGF and EMMPRIN expression in paraffin-embedded specimens gathered from 65 patients with primary osteosarcoma were detected by the method of immunohistochemistry using antibodies against VEGF and EMMPRIN. The correlation of VEGF and EMMPRIN expression with the clinicopathologic features and with the survival of osteosarcoma was subsequently assessed.

Results

The expression of VEGF and EMMPRIN was detected in 47/65 (72.31%) and 45/65 (69.23%) of patients with osteosarcoma, respectively. Positive expression of VEGF and EMMPRIN was significantly correlated with surgical stage and percentage of dead cells of osteosarcoma. A significant correlation was found between the expression of VEGF and EMMPRIN in osteosarcoma (r = 0.89, p = 0.01). Additionally, surgical stage, percentage of dead cells, VEGF and EMMPRIN expression showed significant influence on overall survival (OS) and disease-free survival (DFS) in univariate analysis. In multivariate analysis, surgical stage (IIA versus IIB/III) and percentage of dead cells (≤90% versus >90%) were significant for DFS and OS. Those patients with VEGF+/EMMPRIN+ co-expression showed significantly shorter OS and DFS compared with VEGF−/EMMPRIN− expression.

Conclusion

According to our study, the overexpression of VEGF or EMMPRIN may be an important feature of osteosarcoma. A combined detection of VEGF/EMMPRIN co-expression may benefit us in prediction of a poor survival of osteosarcoma.     

Dealing with the family: CD147 interactions with cyclophilins

CD147 is a widely expressed plasma membrane protein that has been implicated in a variety of physiological and pathological activities. It is best known for its ability to function as extracellular matrix metalloproteinase inducer (hence the other name for this protein, EMMPRIN), but has also been shown to regulate lymphocyte responsiveness, monocarboxylate transporter expression and spermatogenesis. These functions reflect multiple interacting partners of CD147. Recently, interaction of CD147 with proteins of the cyclophilin family has been demonstrated and activity of CD147 as a signalling receptor to extracellular cyclophilins A and B has been shown. Given that extracellular cyclophilins are potent chemotactic agents for various immune cells, further studies of the role of cyclophilin-CD147 interaction in inflammation followed. They demonstrated that agents targeting CD147 or cyclophilin had a significant anti-inflammatory effect in animal models of acute or chronic lung diseases and rheumatoid arthritis. Here, we review the current knowledge about interactions between CD147 and cyclophilins.     

视网膜母细胞瘤和正常视网膜组织中基质调控蛋白表达及其意义(英文)

目的:研究视网膜母细胞瘤(RB)和正常视网膜组织中EMMPRIN、MMP1、MMP9和TIMP2表达水平及其临床病理意义和相互联系。方法:收集30例RB眼球摘除手术标本和15例正常视网膜组织标本。常规制作石蜡包埋切片,EMMPRIN、MMP1、MMP9和TIMP2染色方法均为Envision免疫组织化学法。结果:RB组织中EMMPRIN、MMP1、MMP9表达阳性率均高于正常视网膜组织(P<0.01),TIMP2则低于正常视网膜组织(P<0.01)。临床分期I期、分化型、未侵犯视神经及生存期≥2aRB病例EMMPRIN、MMP1、MMP9表达阳性率低于临床分期III期、未分化型、侵犯视神经和生存<2a病例(P<0.05或P<0.01);分化型、未侵犯视神经及生存期≥2aRB病例TIMP2表达阳性率明显高于未分化型、侵犯视神经和生存<2a病例(P<0.05或P<0.01);RB中,EMMPRIN、MMP1、MMP9表达呈高度一致性(P<0.05),TIMP2与EMMPRIN、MMP1、MMP9表达水平呈高度不一致性(P<0.05)。结论:EMMPRIN、MMP1、MMP9和TIMP2的表达水平可能是反映RB进展、侵袭能力及预后的重要标记物,它们之间存在着内在的相互调控关系。     

细胞外基质金属蛋白酶诱导因子及金属蛋白酶-2 表达与鼻咽癌淋巴结转移的关系

目的:研究细胞外基质金属蛋白酶诱导因子(EMMPRIN)和基质金属蛋白酶-2(MMP-2)蛋白表达与鼻咽癌淋巴结转移的关系.方法:免疫组化法检测鼻咽慢性炎症组、无转移组鼻咽癌、转移组鼻咽癌原发灶及其颈部淋巴结转移灶内EMMPRIN与MMP-2蛋白的表达.结果:1)EMMPRIN蛋白在慢性炎症组、无转移组鼻咽癌、转移组鼻咽癌原发灶及其颈部淋巴结转移灶的表达阳性率分别为13.3%(2/15)、30.0%(6/20)、66.7%(22/33)和81.8%(27/33),在慢性炎症组与转移组鼻咽癌原发灶间、无转移组与转移组鼻咽癌原发灶间、转移组鼻咽癌原发灶与淋巴结转移灶间的差异均有显著性(P均≤0.01),而且转移组鼻咽癌原发灶及颈部淋巴结转移灶内EMMPRIN表达强度均强于无转移组(P均＜0.05);2)MMP-2蛋白在鼻咽慢性炎症组、无转移组鼻咽癌、转移组鼻咽癌原发灶及颈部淋巴结转移灶表达阳性率分别为13.3%(2/15)、35.0%(7/20)、60.6%(20/33)、72.7%(24/33),在慢性炎症组与转移组鼻咽癌原发灶间、转移组鼻咽癌原发灶与颈部淋巴结转移灶间的差异有显著性(P均＜0.01);3)鼻咽癌组织内EMMPRIN与MMP-2的蛋白表达呈正相关(rs=0.466,P＜0.01).结论:EMMPRIN蛋白的过度表达是鼻咽癌淋巴结转移发生的重要因素,可作为预测判断鼻咽癌发生淋巴结转移的重要参考指标之一;MMP-2蛋白的过度表达是促进鼻咽癌转移的重要因素.     

EMMPRIN和MMP-2的表达与原发性肺癌临床病理学的关系

目的:探讨原发性肺癌组织EMMPRIN和MMP-2蛋白的表达及其临床意义。方法:选取原发性肺癌患者116例,以正常肺组织38例作为对照,应用SP免疫组化方法检测EMMPRIN和MMP-2蛋白的表达。结果:原发性肺癌组织EMM-PRIN和MMP2蛋白的阳性表达率分别为71.6%(83/116)和69.8%(81/116),明显高于正常肺组织中的阳性表达率(5.3%和21.1%,P<0.01)。EMMPRIN和MMP2在中、低分化癌中的强阳性表达率高于高分化癌(P<0.05);在淋巴结转移组的强阳性率高于无淋巴结转移组(P<0.01);但二者的表达与肿瘤大小、组织学分型无明显关联。Spearman等级相关性检验分析表明原发性肺癌组织中EMMPRIN的表达和MMP2的表达之间呈正相关(r=0.729,P<0.01)。结论:EMMPRIN和MMP-2蛋白的过度表达与原发性肺癌的发生、浸润、转移有关,可作为新的原发性肺癌标记物用于联合检测,为临床治疗该肿瘤提供新的策略和方案。     

CD147 immunoglobulin superfamily receptor function and role in pathology

The immunoglobulin superfamily member CD147 plays an important role in fetal, neuronal, lymphocyte and extracellular matrix development. Here we review the current understanding of CD147 expression and protein interactions with regard to CD147 function and its role in pathologic conditions including heart disease, Alzheimer's disease, stroke and cancer. A model linking hypoxic conditions found within the tumor microenvironment to upregulation of CD147 expression and tumor progression is introduced.     

Distribution of CD147 During Enteropathogenic Escherichia coli and Salmonella enterica Serovar Typhimurium Infections

Enteropathogenic Escherichia coli (EPEC) and Salmonella enterica serovar Typhimurium (S. Typhimurium) are highly infectious gastrointestinal human pathogens. These microbes inject bacterial-derived effector proteins directly into the host cell cytosol as part of their disease processes. A common host subcellular target of these pathogens is the actin cytoskeleton, which is commandeered by the bacteria and is used during their attachment onto (EPEC) or invasion into (S. Typhimurium) the host cells. We previously demonstrated that the host enzyme cyclophilin A (CypA) is recruited to the actin-rich regions of EPEC pedestals and S. Typhimurium membrane ruffles. To further expand the growing catalogue of host proteins usurped by actin-hijacking bacteria, we examined the host plasma membrane protein and cognate receptor of CypA, CD147, during EPEC and S. Typhimurium infections. Here, we show that CD147 is enriched at the basolateral regions of pedestals but, unlike CypA, it is absent from their actin-rich core. We show that the CD147 recruitment to these areas requires EPEC pedestal formation and not solely bacteria-host cell contact. Additionally, we demonstrate that the depletion of CD147 by siRNA does not alter the formation of pedestals. Finally, we show that CD147 is also a component of actin-rich membrane ruffles generated during S. Typhimurium invasion of host cells. Collectively, our findings establish CD147 as another host component present at dynamic actin-rich structures formed during bacterial infections. Anat Rec, 302:2224–2232, 2019. © 2019 American Association for Anatomy     

子宫内膜异位症患者血清基质金属蛋白酶-9及其诱导因子血管内皮生长因子的变化

目的探讨细胞外基质金属蛋白酶诱导因子（EMMPRIN）、基质金属蛋白酶-9（MMP-9）、血管内皮生长因子（VEGF）在子宫内膜异位症患者血清中表达水平的变化及其临床意义。方法收集70例子宫内膜异位症（EMs）患者（其中Ⅰ期10例、Ⅱ期14例、Ⅲ期28例、Ⅳ期18例）和20例对照组患者的血清,以及30例EMs患者手术加药物治疗后的血清标本,采用酶联免疫吸附法（ELISA）定量检测血清中EMMPRIN、MMP-9、VEGF的表达水平。结果EMs患者血清中三者的表达水平高于对照组（P〈0.05）,早期患者（Ⅰ~Ⅱ期）血清中三者低于Ⅲ~Ⅳ期（P〈0.05）;手术加药物治疗后EMs患者血清VEGF水平可显著性降低;血清VEGF水平与临床分期呈直线正相关关系（P〈0.05,r=0.396）。结论EMMPRIN、MMP-9、VEGF在EMs发病中起着重要作用,检测血清中VEGF水平对于EMs患者随访监测及评价临床疗效有一定价值。