Increased expression of MUC18 correlates with the metastatic progression of mouse prostate adenocarcinoma in the TRAMP model
Increased expression of MUC18 correlates with the metastatic progression of mouse prostate adenocarcinoma in the TRAMP model
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DOI：
10.1097/01.ju.0000154643.30048.2c
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发表时间：
2005-05-01
影响因子：
6.6
通讯作者：
Wu, MWH
中科院分区：
文献类型：
--
作者：
Wu, GJ;Fu, PP;Wu, MWH
目的：转基因小鼠前列腺腺癌（TRAMP）模型是密切模拟临床前列腺癌进展的范例。我们之前报道过MUC18是Ig基因超家族中的一种细胞粘附分子，是人类前列腺癌细胞转移潜力的标志物和重要介质。在本研究中，我们研究了 TRAMP 模型中 MUC18 表达增加与前列腺癌恶性进展的可能相关性。 材料和方法：我们使用免疫组织化学、蛋白质印迹和逆转录聚合酶链反应分析来确定前列腺肿瘤大小为 0.4 至 12.7 的 178 至 282 日龄 TRAMP 阳性男性前列腺中 MUC18 的表达。 通用汽车。 8 个正常前列腺、10 个患有高级别前列腺上皮内瘤变 (PIN) 的前列腺、24 个患有原发性前列腺癌的前列腺、来自 50 只纯 C57BL/6 TRAMP 小鼠（Wu 群体）的 10 个转移性病灶和 2 个正常前列腺、2 个具有高级别 PIN 的前列腺、6 个患有原发性前列腺癌的前列腺和来自 10 只 [C57BL/6 TRAMP x FVB] 的 4 个转移性病灶 使用F1小鼠（NMG集落）。结果：我们发现小鼠MUC18在所有（100%）高级别PIN、腺癌和转移病灶中表达。所有携带原发性前列腺肿瘤的小鼠的前列腺癌均已转移至主动脉周围淋巴结，有些小鼠已转移至其他器官（肝、肺、肾、睾丸、精囊和腹腔）。相比之下，来自10个非转基因同窝小鼠的前列腺没有可检测到的MUC18表达。结论：MUC18表达在TRAMP模型中上调，并且与该转基因模型中小鼠前列腺腺癌的恶性进展相关。这进一步证实了MUC18在增加前列腺癌细胞的转移潜力方面具有重要作用的假设。
Purpose: The transgenic adenocarcinoma mouse prostate (TRAMP) model is a paradigm that closely mimics the progression of clinical prostate cancer. We have previously reported that MUC18, a cell adhesion molecule in the Ig gene superfamily, is a marker as well as an important mediator for the metastatic potential of human prostate cancer cells. In this study we investigated the possible correlation of increased MUC18 expression with the malignant progression of prostate cancer in the TRAMP model.Materials and Methods: We used immunohistochemistry, Western blot and reverse transcriptase-polymerase chain reaction analyses to determine MUC18 expression in the prostate gland of 178 to 282-day-old TRAMP positive males with a prostate tumor size of 0.4 to 12.7 gm. Eight normal prostates, 10 prostates with high grade prostatic intraepithelial neoplasia (PIN), 24 prostates with primary prostate cancer, 10 metastatic lesions from 50 pure C57BL/6 TRAMP mice (Wu colony) and 2 normal prostates, 2 prostates with high grade PIN, 6 prostates with primary prostate cancer and 4 metastatic lesions from 10 [C57BL/6 TRAMP x FVB] F1 mice (NMG colony) were used.Results: We found that mouse MUC18 was expressed in all (100%) high grade PIN, adenocarcinomas and metastatic lesions. All mice bearing primary prostate tumors had prostate cancer metastatic to the peri-aortic lymph nodes and some had it to other organs (liver, lung, kidney, testes, seminal vesicles and abdominal cavity). In contrast, prostates from 10 nontransgenic littermates did not have detectable MUC18 expression.Conclusions: MUC18 expression is up-regulated in the TRAMP model and it correlates with the malignant progression of mouse prostate adenocarcinoma in this transgenic model. This further strengthens the hypothesis that MUC18 has an important role in increasing the metastatic potential of prostate cancer cells.