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犬乳腺肿瘤中与硫酸软骨素相关的多功能蛋白聚糖的免疫组织化学评估

Immunohistochemical evaluation of versican, in relation to chondroitin sulphate, in canine mammary tumours.

作者信息

Erdélyi I, Nieskens D H M, Van Dijk J E, Vass L, Nederbragt H

机构信息

Department of Pathobiology, Faculty of Veterinary Medicine, Utretcht University, Utrecht, The Netherlands.

出版信息

Histol Histopathol. 2003 Oct;18(4):1067-80. doi: 10.14670/HH-18.1067.

Abstract

The expression of increased amounts of versican, a chondroitin sulphate proteoglycan, in neoplastic tissues may play a role in promoting tumour cell proliferation and migration. This study investigated the immunolocalization of versican in normal and neoplastic canine mammary tissues, using antibodies 12C5 and 2B1, against different epitopes of the protein core of versican. Antibody CS56, recognising chondroitin sulphate (CS), was used to investigate the relation between versican and CS, which accumulates in canine mammary tumours. We found enhanced versican expression in both benign and malignant tumours, appearing in three main patterns: in periductal tissues, probably in association with basement membranes of ducts; in peripheral invasive areas of malignant tumours; and in spindle cell proliferations and myxoid areas of complex and mixed tumours. The 12C5 and 2B1 immunoreactivities co-localised in all types of tumours, and could be improved by chondroitinase digestion. The only exception was the abundant extracellular matrix (ECM) of spindle cell proliferations, particularly in myxoid areas of complex and mixed tumours, which displayed intense and diffuse 12C5 immunoreactivity and patchy or absent 2B1 and CS56 immunoreactivities; versican immunoreactivity could not be enhanced by chondroitinase digestion. The results indicate that versican is one of the extracellular matrix components characteristic of canine mammary tumours. It appears likely that in complex and mixed tumours versican exists in at least two forms, one of them lacking the CS attachment domain and the 2B1 epitope. Furthermore, the enhanced versican expression in the invasive areas of malignant tumours indicates the involvement of this proteoglycan in tumour cell invasion.

摘要

多功能蛋白聚糖(一种硫酸软骨素蛋白聚糖)在肿瘤组织中表达量增加,可能在促进肿瘤细胞增殖和迁移中发挥作用。本研究使用针对多功能蛋白聚糖蛋白核心不同表位的抗体12C5和2B1,调查了多功能蛋白聚糖在正常和肿瘤性犬乳腺组织中的免疫定位。识别硫酸软骨素(CS)的抗体CS56用于研究多功能蛋白聚糖与CS之间的关系,CS在犬乳腺肿瘤中会蓄积。我们发现良性和恶性肿瘤中多功能蛋白聚糖表达均增强,呈现三种主要模式:在导管周围组织中,可能与导管基底膜有关;在恶性肿瘤的外周浸润区域;以及在复杂和混合性肿瘤的梭形细胞增殖和黏液样区域。12C5和2B1免疫反应性在所有类型肿瘤中均共定位,且可通过软骨素酶消化得到增强。唯一的例外是梭形细胞增殖的丰富细胞外基质(ECM),特别是在复杂和混合性肿瘤的黏液样区域,其显示强烈且弥漫的12C5免疫反应性以及斑片状或无2B1和CS56免疫反应性;多功能蛋白聚糖免疫反应性不能通过软骨素酶消化增强。结果表明多功能蛋白聚糖是犬乳腺肿瘤特征性的细胞外基质成分之一。在复杂和混合性肿瘤中,多功能蛋白聚糖似乎至少以两种形式存在,其中一种缺乏CS附着结构域和2B1表位。此外,恶性肿瘤浸润区域中多功能蛋白聚糖表达增强表明该蛋白聚糖参与肿瘤细胞侵袭。

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