Faculty of Veterinary Medicine, University of Teramo, Teramo, Italy.
School of Veterinary Science, The University of Queensland, Brisbane, Queensland, Australia.
Vet Comp Oncol. 2019 Sep;17(3):298-307. doi: 10.1111/vco.12469. Epub 2019 Apr 8.
Nectin-4 is an E-cadherin-based adherens junction protein of normal epithelial cells, as well as a potent mediator of anchorage-independent cancer colony formation. It is considered a tumour-associated histological and serological marker in various human cancers. The transcription factor p63 is a basal cell marker in the normal prostate, involved in cell adhesion, as well as in the formation and survival of circulating tumour cell clusters. The aim of this study was to evaluate Nectin-4 and p63 immunohistochemical expression in 42 canine prostate tissues including 2 normal prostates, 10 benign prostatic hyperplasias (BPHs), 30 prostatic carcinomas (PCs), 1 pulmonary and 1 lymph node metastasis. From normal to neoplastic tissues, Nectin-4 showed a progressive switching from membranous (m-Nectin-4) to cytoplasmic (c-Nectin-4), regardless of the histological subtypes, except for lack of expression in solid PCs. Metastatic cells exhibited both strong membranous and cytoplasmic positivity. c-Nectin-4 expression was significantly (P < 0.0001) increased in PCs/metastasis compared to BPHs cases and a decrease (P < 0.05) of nuclear p63 immunostaining was also detected in the two groups. Furthermore, data showed a significant association (P < 0.05) between p63 and m-Nectin-4 distribution, although their colocalization was detected only in scattered cells by double immunofluorescence. Our results suggest the involvement of m-Nectin-4 in canine prostate tumourigenesis and metastatic potential, while the exact role of c-Nectin-4 expression detectable in primary PCs requires further investigations.
黏附连接蛋白 4 是正常上皮细胞中 E-钙黏蛋白为基础的黏附连接蛋白，也是锚定非依赖性肿瘤集落形成的有力介质。它被认为是各种人类癌症中与肿瘤相关的组织学和血清学标志物。转录因子 p63 是正常前列腺中的基底细胞标志物，参与细胞黏附以及循环肿瘤细胞簇的形成和存活。本研究旨在评估 42 份犬前列腺组织（包括 2 份正常前列腺、10 份良性前列腺增生（BPH）、30 份前列腺癌（PC）、1 份肺转移和 1 份淋巴结转移）中黏附连接蛋白 4 和 p63 的免疫组织化学表达。从正常组织到肿瘤组织，Nectin-4 表现出从膜性（m-Nectin-4）到细胞质（c-Nectin-4）的逐渐转换，无论组织学亚型如何，除了实体性 PC 缺乏表达外。转移性细胞表现出强烈的膜性和细胞质阳性。与 BPH 相比，PC/转移中的 c-Nectin-4 表达显著增加（P<0.0001），并且在两组中还检测到核 p63 免疫染色减少（P<0.05）。此外，数据显示 p63 和 m-Nectin-4 分布之间存在显著相关性（P<0.05），尽管通过双重免疫荧光仅在散在细胞中检测到它们的共定位。我们的结果表明 m-Nectin-4 参与犬前列腺肿瘤发生和转移潜能，而在原发性 PC 中可检测到的 c-Nectin-4 表达的确切作用需要进一步研究。
