Expression of 67-kDa laminin receptor was associated with tumor progression and poor prognosis in epithelial ovarian cancer

Objective

67-kDa laminin receptor (67LR) has been identified as a prognostic biomarker for a variety of human cancers. We investigated the clinical significance of 67LR expression and its functional role in epithelial ovarian cancer (EOC).

Methods

67LR expression was evaluated by immunohistochemistry in 62 patients with EOC. We assessed the correlation of 67LR expression with clinical characteristics. In vitro experiment was performed for 67LR with inhibition using siRNA to evaluate its role in cell survival, apoptosis, and invasion in EOC cells.

Results

67LR was predominantly expressed on the cell membrane in the majority of EOC samples (45/62, 73%). 67LR expression was significantly correlated with advanced stage (P = 0.001). Patients with 67LR expression had shorter progression-free survival among all the patients (P = 0.010) and in particular among patients with advanced stages (P = 0.046). When 67LR expression was inhibited by siRNA in EOC cells (HeyA8 and A2780), there was a significant decrease of cell proliferation and invasion as well as increase of apoptosis.

Conclusion

These findings suggest that 67LR expression may play an important role in tumor progression into advanced stage with poor prognosis in EOC and down-regulation of 67LR on tumor cells may be a therapeutic target in those patients.     

层黏连蛋白及其受体与头颈部肿瘤浸润转移的关系

层黏连蛋白是细胞外基质中的非胶原糖蛋白,生理状态下调节一系列生物现象,包括细胞黏附、生长、形态发生及移动等,而在肿瘤的侵袭过程中,则对癌细胞的黏附、移动起着重要作用。     

层粘连蛋白在乙肝相关性肝癌中的表达、分布及意义

 目的 探讨层粘连蛋白(laminin,LN)在乙型肝炎病毒 (hepatitis Bvirus,HBV) 感染相关性肝癌(hepatocellular carcinoma,HCC)中的表达分布及意义。方法 选取2003-01至2013-05在武警总医院施行了原位肝移植手术的215例HBV相关性HCC伴肝硬化患者的组织标本,应用免疫组化的方法检测LN在肝癌组织和癌旁组织中的表达情况,并以30例正常肝组织和良性肝病组作为对照。结果 LN主要定位于HBV相关性肝癌组织肝窦窦壁,其次为癌旁间质血管与新生血管及细胞膜/浆。LN在肝癌组织中肝窦窦壁和新生血管的阳性表达率为70.23％(151/215),在癌旁组织和良性肝病中肝窦窦壁和新生血管的阳性表达率分别为57.20％(123/215)和13.33％(3/30),LN在癌组织中的表达显著高于其在癌旁及良性肝病中的表达(P=0.000),LN在癌组织中的阳性表达与微卫星灶(P=0.026)、肿瘤数量(P=0.053)、血管侵犯(P=0.005)、TNM分期(P=0.029)显著相关。结论 LN的过表达可能与肝癌的发生发展及侵袭转移相关。
     

Assessment of seminal plasma laminin in fertile and infertile men

Aim： To assess laminin levels in the seminal plasma of infertile and fertile men, and to analyze the correlation of laminin levels with sperm count, age, sperm motility and semen volume. Methods： One hundred and twenty-five recruited men were equally divided into five groups according to their sperm concentration and clinical examination： fertile normozoospermia, oligoasthenozoospermia, non-obstructive azoospermia （NOA）, obstructive azoospermia （OA） and congenital bilateral absent vas deferens （CBAVD）. The patients＇ medical history was investigated and patients underwent clinical examination, conventional semen analysis and estimation of seminal plasma laminin by radioimmunoassay. Results： Seminal plasma laminin levels of successive groups were： 2.82 ± 0.62, 2.49 ± 0.44, 1.77 ± 0.56, 1.72 ± 0.76, 1.35 ± 0.63 U/mL, respectively. The fertile normozoospermic group showed the highest concentration compared to all infertile groups with significant differences compared to azoospermic groups （P 〈 0.05）. Testicular contribution was estimated to be approximately one-third of the seminal laminin. Seminal plasma laminin demonstrated significant correlation with sperm concentration （r = 0.460, P 〈 0.001） and nonsignificant correlation with age （r = 0.021, P = 0.940）, sperm motility percentage （r = 0.142, P = 0.615） and semen volume （r = 0.035, P = 0.087）. Conelusion： Seminal plasma laminin is derived mostly from prostatic and testicular portions and minimally from the seminal vesicle and vas deferens. Estimating seminal laminin alone is not conclusive in diagnosing different cases of male infertility.     

丹蒲胶囊对试验性慢性前列腺炎的病理学和免疫组织化学研究

目的 探讨丹蒲胶囊治疗慢性前列腺炎的作用机理。方法 对实验性大鼠前列腺组织进行组织病理学和纤维连接蛋白（FN）、层粘连蛋白（LN）免疫组织化学的观察。结果 丹蒲胶囊可明显抑制大鼠慢性前列腺炎组织中的炎细胞浸润和间质纤维组织增生，并促使前列腺腺腔扩大，腔内分泌物增多，丹蒲胶囊组与模型组相比，有显著性差异（P＜0．05）。丹蒲胶囊组与模型组的FN表达均呈弱阳性，两组相比，无显著性差异（P＞0．05）；丹蒲胶囊组的LN表达主要呈弱阳性，模型组的LN表达呈强阳性和阳性，两组相比，有显著性差异（P＜0．05）。结论 丹蒲胶囊具有明显抗炎、抗纤维化及增强腺细胞的分泌功能。FN、LN在前列腺炎发病中起重要作用，LN可作为判断慢性前列腺炎的炎症及纤维化程度的参考指标，丹蒲胶囊可显著降低大鼠慢性前列腺炎组织内的LN水平。     

细胞外基质金属蛋白酶诱导因子和层黏连蛋白受体在人脑胶质瘤中的表达及意义

目的 探讨细胞外基质金属蛋白酶诱导因子(CD147)和层黏连蛋白受体(LN-R)在胶质瘤中的表达及意义.方法 采用RT-PCR对48例人脑胶质瘤组织的CD147和LN-R的mRNA表达情况进行半定量分析.结果 胶质瘤CD147和LN-R mRNA的阳性表达率分别为66.67%和58.33%,联合表达率为56.25%,两者之间存在正相关(r=0.815,P＜0.01).随着胶质瘤级别增高、侵袭能力增强,CD147和LN-R的mRNA表达水平也相应增高.结论 CD147和LN-R表达与胶质瘤恶性程度密切相关,其可作为判断胶质瘤病人临床预后和治疗有效的参考指标.     

纤维连结蛋白、Ⅳ型胶原和层粘连蛋白在浸润性乳腺癌组织中的表达及意义

用免疫组化法观察了层粘连蛋白（ＬＮ）、Ⅳ型胶原（Ｃｏｌ）和纤维连结蛋白（ＦＮ）在１１３例浸润性乳腺癌和其中３７例淋巴结转移癌组织中的表达。结果表明，这３种蛋白均可在原位癌结构的基底膜处呈连续状表达。其中ＣｏｌⅣ和ＬＮ平均积分光密度均高于它们在正常小叶基底膜的表达（Ｐ＜０．０５）。３种蛋白在浸润性癌巢周均可表达（表达率为ＬＮ３８．６％，ＣｏｌⅣ２３．９％，ＦＮ８４．１％），ＣｏｌⅣ和ＬＮ的表达有相关性（Ｐ＜０．０５）。ＦＮ在浸润癌间质中表达与患者预后密切相关（Ｐ＜０．０１）。它们在癌细胞内亦可表达（ＣｏｌⅣ１９．４７％、ＬＮ２７．４％、ＦＮ２７．４％），其中ＦＮ与浸润性导管癌和肿瘤体积大小有关。淋巴结转移癌巢旁和细胞内（ＬＮ１３．５％，ＣｏｌⅣ８．５％，ＦＮ３３．３％）也可见到它们表达，ＦＮ在转移癌细胞内的表达率明显高于其它２种蛋白（Ｐ＜０．０１），且与原位癌灶细胞内的表达有关（Ｐ＜０．０２）。表明：癌细胞本身有合成基底膜物质的能力；ＦＮ在乳腺癌间质中的表达与预后较好有联系。     

Immunocytochemical detection of basement membrane antigens in the histopathological evaluation of laryngeal dysplasia and neoplasia

Immunocytochemical detection of intrinsic components of the basement membrane (type IV collagen and laminin) was performed in biopsies of carcinoma in situ, dysplasia and hyperplasia of the laryngeal mucosa. We found a distinct and continuous basement membrane, containing both laminin and type IV collagen, at the border between epithelial cells and mesenchymal stroma in normal as well as in hyperplastic and dysplastic mucosa. In contrast, irregular discontinuities were found in some cases of carcinoma in situ and in invasive carcinoma. In addition, immunoreactivity for intracytoplasmic basement membrane components was noticed occasionally in neoplastic epithelial cells. In areas of inflammation, infiltration of leucocytes into the epithelium was occasionally accompanied by sharply defined small interruptions of the basement membrane. Our results indicate that immunohistochemical detection of basement membrane components can be of value for the demonstration of microinvasive growth in laryngeal cancer.     

Expression of integrins by human trophoblast and differential adhesion to laminin or fibronectin

The process of placental implantation involves a series of transformationsof trophoblast from a single polarized epithelial layer restingon a basement membrane (villous trophoblast), to cellular aggregates(trophoblast columns) which ultimately disperse to invade uterinedecidua as individual cells (interstitial trophoblast). Suchtissue re-modelling is associated with changes in the constituentsof the extracellular matrix and in the expression of matrixreceptors by the cells, the most relevant being the family ofintegrins which bind to laminin and fibronectin. In this studywe show, by immunohistology and flow cytometry, a gradual lossof laminin receptors with the concomitant acquisition of fibronectinreceptors as trophoblast is transformed from the villous phenotype,through the cell columns, into the extravillous population.The pattern of staining for the ₅, ₆, ₁ and ₄ subunits indicatesthat the integrins expressed by trophoblast are predominantlythe ₅₁ and the ₆₄ heterodimers. We have also shown that isolatedtrophoblast cells assume a flattened, sessile phenotype whencultured on laminin but exhibit a more spreading, motile morphologywhen plated on fibronectin. In addition, numerous multinucleatedgiant cells are observed on a fibronectin substrate. Our datasuggest that the relative expression of laminin and fibronectinreceptors may determine the morphology and behaviour of trophoblastduring the process of implantation.     

Effect of the dental adhesive, 4-META/MMA-TBB resin, on adhesion and keratinization of regenerating oral epithelium

Background and Objective:  The 4-META/MMA-TBB [4-(2-methacryloxyethyl)trimellitic anhydride/methyl methacrylate-tributylborane] resin is widely used as a dental adhesive. It has also been applied in the dressing of gingival wound surfaces following periodontal surgery. However, its effect on the regeneration and/or cell attachment of the oral epithelium remains to be clarified. To evaluate the effect of the resin applied as a wound dressing, we investigated expression of laminin 5, integrin β₄ and cytokeratin 14 in regenerating oral epithelium treated with this resin following gingivectomy from the viewpoint of cell attachment and differentiation.
Material and Methods:  The resin was applied to the entire wound surface in rats after gingival surgery, and regenerating epithelium was examined immediately and at 1, 3, 5, 7 and 14 days later. The resin was removed 2 weeks after application in some animals and tissue further examined at 1, 3, 5 and 7 days later.
Results:  Regenerating epithelium under the resin was not keratinized, but became keratinized immediately after removal of the resin. Laminin 5 and integrin β₄ were immunolocalized in the basal lamina, the internal basal lamina, in marginal cells of the regenerating epithelium and at the resin–regenerating epithelium interface. Cytokeratin 14 localized in the regenerating epithelium underneath the resin, as well as in healthy and regenerated junctional epithelial cells.
Conclusion:  These results suggest that this resin covers the wound surface and that the regenerating epithelium biologically adheres to the resin during the initial process of its regeneration.