Role of canine basal cells in prostatic post natal development, induction of hyperplasia, sex hormone-stimulated growth; and the ductal origin of carcinoma
Role of canine basal cells in prostatic post natal development, induction of hyperplasia, sex hormone-stimulated growth; and the ductal origin of carcinoma
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DOI：
10.1002/pros.1058
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发表时间：
2001-05-15
期刊：
影响因子：
2.8
通讯作者：
Alroy, J
中科院分区：
文献类型：
--
作者：
Leav, I;Schelling, KH;Alroy, J
背景犬的前列腺经常被提议作为人类腺体异常生长的模型。前列腺增生在老年男性中很常见，据估计，100%的老年完整犬都存在前列腺增生。虽然前列腺癌在老年男性中很常见，但在狗中似乎很罕见，与人类疾病不同，它在去势动物中发生的频率相对较高。由于基底细胞被认为是人类腺体正常和异常生长的关键参与者，我们使用免疫组织化学来研究它们在犬前列腺发育、增生和癌的演变以及性激素对这些细胞的影响中可能发挥的作用。从7只性不成熟的犬尸检时获得前列腺标本，从14只性成熟的完整动物、4只去势犬和19只前列腺癌犬的尸检和活检标本获得前列腺标本。此外，我们还研究了用5 α-双氢睾酮（DHT）治疗6个月的两只完整狗和随后用5 α-雄甾烷-3 α二醇和雌二醇-17 α治疗的两只去势狗的前列腺。以及来自给予DHT 2周的2只性切除动物的标本。所有标本均行高分子量细胞角蛋白（HMC）、泛细胞角蛋白（Pancytokeratin）、雄激素受体（AR）和增殖标记物KI-67的免疫组化染色。我们发现，基底细胞是新生和成年犬前列腺的主要增殖细胞类型，HMC染色的表达，它定义了这些细胞，可能是由雄激素调节。在成年腺体中，导管基底细胞形成连续层，而内衬腺泡不连续。这两种基底细胞类型的人口是CANAR阳性，但虽然HMC免疫染色被废除后，长期去势腺泡细胞，染色仍然在导管细胞对应。随着增生的组织学发展，腺泡基底细胞群随着年龄的增长而增加，并且是表达KI-67的主要细胞类型。相反，在老年狗的前列腺中，导管基底细胞群没有扩增，并且很少被KI-67阳性染色。HMC的数量。和KI-67-染色的腺泡基底细胞显着增加，在前列腺的完整的狗与DHT治疗时，与未处理的对照腺体相比。而导管基底细胞则不然。雄激素单独或与雌激素一起给去势犬诱导广泛的HMC和KI-67免疫染色在两个群体的基底细胞。此外，我们的研究结果表明，大多数犬前列腺癌可能只产生于导管上皮。19例癌中仅1例含有表达AR的细胞，这表明雄激素在这些癌的发生或发展中不是必需的。我们的研究结果表明，两个生物学上不同的群体的基底细胞mall存在于犬前列腺。在这方面，与年龄相关的增殖腺泡基底细胞群的扩张，可能是由性类固醇介导的，是犬前列腺增生发病机制的关键因素。此外，我们发现狗的前列腺癌可能起源于导管细胞。总之，这些发现可能表明，犬腺泡基底细胞和导管上皮细胞有单独的易感性的因素，促进增生或肿瘤的发展。前列腺47：149-163，2001年。(C)2001 Wiley-Liss，Inc.
BACKGROUND. The canine prostate has often been proposed as a model for abnormal growth of the human gland. Hyperplasia of the prostate is common in aging men and has been estimated to be present in 100% of old intact dogs. While prostatic carcinoma is common in older men it appears to be rare in dogs and unlike the disease in humans it occurs with relatively high frequency in castrated animals. Since basal cells are thought to be key participants in normal and abnormal growth of the human gland, we used immunohistochemistry to investigate the role that they may play in canine prostatic development, the evolution of hyperplasia and carcinoma, and the effects of sex hormones on these cells.METHODS. Prostate specimens were obtained at autopsy from seven sexually immature dogs, autopsy and biopsy samples from 14 sexually mature intact animals, from four castrates, and from19 dogs with prostatic carcinoma. In addition, we also studied the prostates from two intact dogs treated with 5 alpha -dihydrotestosterone (DHT) for 6 months and two castrated dogs that were subsequently treated with 5 alpha -androstane-3 alpha diol and estradiol-17 alpha. as well as specimens from two sexually ablated animals given DHT for 2 weeks. All specimens were immunostained for high molecular weight cytokeratin (HMC), Pancytokeratin, androgen receptor (AR), and the proliferative marker KI-67.RESULTS. Wa find that basal cells are the major proliferative cell type in the neonatal and adult canine prostate and that the expression of HMC staining, which defines these cells, may be regulated by androgens. In the adult gland, ductal basal cells formed a contiguous layer whereas those lining acini were discontinuous. Populations of both basal cell types ere variably AR positive but while HMC immunostaining was abolished in acinar cells following long-term castration, staining remained in ductal cell counterparts. Paralleling the histological development of hyperplasia, the acinar basal cell population increased with age and were the major cell type that expressed KI-67. in contrast, ductal basal cell populations did not expand in the prostates of older dogs and were seldom positively stained for KI-67. The numbers of HMC. and KI-67-stained acinar basal cells were dramatically increased in the prostates of intact dogs treated with DHT when compared with glands of untreated controls. This was not the case with ductal basal cells. Androgens given alone or together with estrogen to castrated dogs induced widespread HMC and KI-67 immunostaining in both populations of basal cells. In addition, our results indicate that the majority of canine prostatic carcinomas likely arise exclusively from ductal epithelium. Only one of the 19 cases of carcinoma contained cells that expressed AR which suggests that androgens ma; not be required for the initiation or progression of these cancers.CONCLUSIONS. Our findings indicate that two biologically distinct populations of basal cells mall exist in the canine prostate. In this regard the age-related expansion of proliferating acinar basal cell populations, probably mediated by sex steroids, is a key factor in the pathogenesis of canine prostatic hyperplasia. Additionally we find that prostatic carcinoma in the dog likely arises from ductal cells. Taken together these findings may indicate that canine acinar basal cells and ductal epithelium have separate susceptibilities to factors that promote hyperplastic or neoplastic development. Prostate 47:149-163, 2001. (C) 2001 Wiley-Liss, Inc.