Involvement of Heregulin/HER3 in the Primary Culture of Human Urothelial Cancer
Involvement of Heregulin/HER3 in the Primary Culture of Human Urothelial Cancer
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DOI：
10.1016/j.juro.2012.12.106
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发表时间：
2013-07-01
影响因子：
6.6
通讯作者：
Inoue, Masahiro
中科院分区：
文献类型：
--
作者：
Okuyama, Hiroaki;Yoshida, Takahiro;Inoue, Masahiro
目的：建立一种新的人大肠癌原代培养方法。该方法被称为癌组织来源的球体方法，涉及制备原代癌细胞的多细胞球体，所述原代癌细胞被培养以保持细胞-细胞接触。我们将此方法应用于人尿路上皮cancer.Materials和Methods：癌组织来源的球体制备从异种移植物或原发性人膀胱尿路上皮癌肿瘤以下用于人结直肠癌相同的协议。采用免疫组化、Western blot和聚合酶链反应（polymerase chain reaction.Results）对肿瘤组织来源的球状体进行鉴定。结果：我们建立了原发性膀胱尿路上皮癌的异种移植瘤，并分离培养了肿瘤组织来源的球状体。肿瘤组织来源的球体保留了原始肿瘤和异种移植物的特征。调蛋白促进癌组织起源的球状体生长，PI 3 K和mTOR的抑制剂抑制调蛋白诱导的生长，拉帕替尼而不是厄洛替尼也是如此。我们还制备了来自原发性膀胱尿路上皮癌的癌组织来源的球状体。非肌层浸润性尿路上皮癌肿瘤细胞来源的肿瘤细胞球体的建立成功率为90.7%，肌层浸润性肿瘤细胞来源的肿瘤细胞球体的建立成功率为68.2%。总成功率为84.2%。Heregulin促进生长的原发癌组织来源的球体从4 7 patients.Conclusions：我们报告了一种方法，建立原代培养的人尿路上皮癌细胞。heregulin在源自异种移植物和原发性肿瘤的球体的癌组织中的生长刺激表明针对HER 3信号传导的分子靶向治疗用于人尿路上皮癌的可能性。肿瘤组织来源的球体方法可能有助于为拉帕替尼等分子靶向药物选择患者。
Purpose: We previously established a novel method of human colorectal cancer primary culture. This method, termed the cancer tissue originated spheroid method, involves the preparation of multicellular spheroids of primary cancer cells that are cultured so that cell-cell contact is maintained. We applied this method to human urothelial cancer.Materials and Methods: Cancer tissue originated spheroids were prepared from xenografts or primary human bladder urothelial cancer tumors following the same protocol used for human colorectal cancer. Cancer tissue originated spheroids were characterized using immunohistochemistry, Western blot and polymerase chain reaction.Results: We established a xenograft from a primary bladder urothelial cancer, and isolated and cultured cancer tissue originated spheroids from the xenograft tumor. Cancer tissue originated spheroids retained the characteristics of the original tumor and those of the xenograft. Heregulin promoted cancer tissue originated spheroid growth, and inhibitors of PI3K and mTOR inhibited heregulin induced growth, as did lapatinib but not erlotinib. We also prepared cancer tissue originated spheroids from primary bladder urothelial cancer. The success rate of establishing primary cancer tissue originated spheroids from nonmuscle invasive urothelial cancer was 90.7% and that from muscle invasive cancer was 68.2%. The overall success rate was 84.2%. Heregulin promoted the growth of primary cancer tissue originated spheroids from 4 of 7 patients.Conclusions: We report a method of establishing primary cultures of human urothelial cancer cells. Growth stimulation by heregulin in cancer tissue originated spheroids from xenografts and primary tumors suggests the possibility of molecular targeting therapy against HER3 signaling for human urothelial cancer. The cancer tissue originated spheroid method might be useful for selecting patients for molecular targeting drugs such as lapatinib.