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人化生性乳腺癌与核心蛋白聚糖

Human Metaplastic Breast Carcinoma and Decorin.

作者信息

Boström Pia, Sainio Annele, Eigėlienė Natalja, Jokilammi Anne, Elenius Klaus, Koskivuo Ilkka, Järveläinen Hannu

机构信息

Department of Pathology, University of Turku and Turku University Hospital, Kiinamyllynkatu 10, 20520, Turku, Finland.

Department of Medical Biochemistry and Genetics, University of Turku, Kiinamyllynkatu 10, 20520, Turku, Finland.

出版信息

Cancer Microenviron. 2017 Dec;10(1-3):39-48. doi: 10.1007/s12307-017-0195-8. Epub 2017 Jun 26.

Abstract

Metaplastic breast carcinoma (MBC) is a rare subtype of invasive breast cancer and has poor prognosis. In general, cancers are heterogeneous cellular masses comprised of different cell types and their extracellular matrix (ECM). However, little is known about the composition of the ECM and its constituents in MBC. Decorin is a ubiquitous ECM macromolecule known of its oncosuppressive activity. As such, it provides an intriguing molecule in the development of novel therapeutics for different malignancies such as MBC. In this study, decorin immunoreactivity and the effect of adenoviral decorin cDNA (Ad-DCN) transduction were examined in MBC. Multiple immunohistochemical stainings were used to characterize a massive breast tumour derived from an old woman. Furthermore, three-dimensional (3D) explant cultures derived from the tumour were transduced with Ad-DCN to study the effect of the transduction on the explants. The MBC tumour was shown to be completely negative for decorin immunoreactivity demonstrating that the malignant cells were not able to synthesize decorin. Ad-DCN transduction resulted in a markedly altered cytological phenotype of MBC explants by decreasing the amount of atypical cells and by inhibiting cell proliferation. The results of this study support approaches to develop new, decorin-based adjuvant therapies for MBC.

摘要

化生性乳腺癌(MBC)是浸润性乳腺癌的一种罕见亚型,预后较差。一般来说,癌症是由不同细胞类型及其细胞外基质(ECM)组成的异质性细胞团块。然而,关于MBC中ECM的组成及其成分知之甚少。核心蛋白聚糖是一种普遍存在的ECM大分子,具有抑癌活性。因此,它为开发针对不同恶性肿瘤(如MBC)的新型治疗方法提供了一种引人关注的分子。在本研究中,检测了核心蛋白聚糖免疫反应性以及腺病毒核心蛋白聚糖cDNA(Ad-DCN)转导在MBC中的作用。采用多种免疫组织化学染色对一名老年女性的巨大乳腺肿瘤进行特征分析。此外,用Ad-DCN转导源自该肿瘤的三维(3D)外植体培养物,以研究转导对外植体的影响。结果显示,MBC肿瘤的核心蛋白聚糖免疫反应性完全阴性,表明恶性细胞无法合成核心蛋白聚糖。Ad-DCN转导通过减少非典型细胞数量和抑制细胞增殖,导致MBC外植体的细胞学表型发生明显改变。本研究结果支持开发基于核心蛋白聚糖的新型MBC辅助治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d860/5750199/37abe4402336/12307_2017_195_Fig1_HTML.jpg

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