Eppler Elisabeth, Müller-Gerbl Magdalena, Maly I Piotr
Department of Biomedicine, University of Basel, Basel, Switzerland.
Histol Histopathol. 2017 Aug;32(8):835-849. doi: 10.14670/HH-11-854. Epub 2016 Dec 12.
The tight junction protein claudin-3 is overexpressed in diverse epithelial tumours and is associated with increased survival, progression and motility of tumour cells. Claudin-3 expression profiles are being increasingly used for diagnostic and prognostic tumour classification. Claudin-3 has been identified as a receptor for Clostridium perfringens enterotoxin, which is under consideration for selective lysis of claudin-3-expressing tumours, particularly brain metastases, and other translational medicine uses. However, the localization of claudin-3 in the brain has not been completely elucidated. While claudin-3 in brain tissue adjacent to claudin-3-expressing metastases had been excluded and low or undetectable levels proposed in the CNS, under physiological conditions, in adult human, rat and mouse brains, claudin-3 was exclusively found in choroid plexus epithelium where it is considered an integral component of the blood-cerebrospinal-fluid barrier. We report here the pronounced presence of claudin-3 not only in the nasal region (as described for rat), but also in the mouse olfactory bulb and nerve using immunohistochemistry and Western blot. Claudin-3 was present in the fila olfactoria from the epithelium to the olfactory nerve and in the main and accessory olfactory bulb. We propose that the abundant presence of claudin-3 in the olfactory system, particularly in nerve fibres and the olfactory bulb cone, which we present here, may play a role at the interface of the central and peripheral nervous system, both as barrier and for axonal growth and communication. Thus, claudin-3 should be considered and further explored with regards to treatment approaches addressing the olfactory bulb and nasal region.
紧密连接蛋白claudin-3在多种上皮肿瘤中过度表达，与肿瘤细胞的存活率增加、进展和迁移有关。Claudin-3表达谱越来越多地用于肿瘤的诊断和预后分类。Claudin-3已被确定为产气荚膜梭菌肠毒素的受体，该毒素正被考虑用于选择性裂解表达claudin-3的肿瘤，特别是脑转移瘤以及其他转化医学用途。然而，claudin-3在脑中的定位尚未完全阐明。虽然已排除与表达claudin-3的转移瘤相邻的脑组织中的claudin-3，并提出中枢神经系统中claudin-3水平较低或无法检测到，但在生理条件下，在成年人类、大鼠和小鼠的脑中，claudin-3仅在脉络丛上皮中发现，被认为是血脑脊髓液屏障的一个组成部分。我们在此报告，使用免疫组织化学和蛋白质印迹法，claudin-3不仅在鼻腔区域（如大鼠中所述）有明显存在，而且在小鼠嗅球和神经中也有明显存在。Claudin-3存在于从上皮到嗅神经的嗅丝以及主嗅球和副嗅球中。我们提出，我们在此展示的claudin-3在嗅觉系统中大量存在，特别是在神经纤维和嗅球锥中，可能在中枢和外周神经系统的界面处发挥作用，既是屏障，又参与轴突生长和通讯。因此，在针对嗅球和鼻腔区域的治疗方法中应考虑并进一步探索claudin-3。
