Walker Marjorie M, Ellis Sebastien M, Auza Michael J, Patel Anup, Clark Peter
Division of Investigative Sciences, Department of Histopathology, St Mary's Campus, Imperial College London, London, UK.
Mod Pathol. 2008 Feb;21(2):85-95. doi: 10.1038/modpathol.3800988. Epub 2007 Dec 14.
During the normal turnover of prostate epithelium, stem cells in the basal cell layer produce an intermediate cell population that gives rise to fully differentiated secretory luminal cells. This process is extensively studied in relation to the development of prostate disease, in particular, to elucidate the origin and nature of prostate cancer. We previously showed that the mRNA of a poorly characterised intercellular adhesion molecule, cadherin-10, is strongly expressed in human prostate. Using anticadherin-10 antibodies, immunohistochemistry, and confocal microscopy, we have examined the pattern of cadherin-10 expression in relation to human prostate epithelial differentiation markers (E-cadherin, CD44, and cytokeratins (CK) 14, 18 and 19) in archival paraffin-embedded and fixed-frozen histopathological specimens in individual and serial sections. In non-neoplastic prostate, E-cadherin is expressed by all basal and luminal epithelial cells, while cadherin-10 is variably expressed in luminal cells where it is colocalised with E-cadherin at basolateral plasma membranes. Cadherin-10 is absent in CK14- and/or CD44-positive basal cells, but is expressed in CK18-positive luminal cells (differentiated secretory cells), a subset of CK19-positive intermediate/luminal cells, but not CK19-positive basal cells. Small foci of prostate cancer express E-cadherin, CK19 and CK18, but cadherin-10 expression is low or undetectable. These findings suggest that the expression of cadherin-10 is associated with the later stages of differentiation of luminal secretory cells, indicating a specific role in secretory cell terminal differentiation. While prostate cancer cells express secretory cell markers (eg, CK18, prostate-specific antigen) and the more generally expressed E-cadherin, their failure to express cadherin-10 further emphasises a role for this cadherin in normal prostate organisation and function.
在前列腺上皮的正常更新过程中，基底细胞层中的干细胞产生一个中间细胞群体，该群体可分化为完全分化的分泌性管腔细胞。针对前列腺疾病的发展，尤其是为了阐明前列腺癌的起源和本质，人们对这一过程进行了广泛研究。我们之前发现，一种特征不明的细胞间黏附分子——钙黏蛋白-10的mRNA在人类前列腺中强烈表达。我们使用抗钙黏蛋白-10抗体、免疫组织化学和共聚焦显微镜，在存档的石蜡包埋和固定冷冻组织病理学标本的单个及连续切片中，研究了钙黏蛋白-10与人类前列腺上皮分化标志物（E-钙黏蛋白、CD44以及细胞角蛋白（CK）14、18和19）相关的表达模式。在非肿瘤性前列腺中，所有基底和管腔上皮细胞均表达E-钙黏蛋白，而钙黏蛋白-10在管腔细胞中呈可变表达，且在基底外侧质膜处与E-钙黏蛋白共定位。CK14和/或CD44阳性的基底细胞中不存在钙黏蛋白-10，但在CK18阳性的管腔细胞（分化的分泌细胞）、CK-19阳性的中间/管腔细胞亚群中表达，而在CK19阳性的基底细胞中不表达。前列腺癌的小病灶表达E-钙黏蛋白、CK19和CK18，但钙黏蛋白-10表达较低或无法检测到。这些发现表明，钙黏蛋白-10的表达与管腔分泌细胞的后期分化相关，提示其在分泌细胞终末分化中具有特定作用。虽然前列腺癌细胞表达分泌细胞标志物（如CK18、前列腺特异性抗原）以及更广泛表达的E-钙黏蛋白，但它们未能表达钙黏蛋白-10，这进一步强调了这种钙黏蛋白在正常前列腺组织和功能中的作用。
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