Department of Pathology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
J Urol. 2013 Jul;190(1):302-10. doi: 10.1016/j.juro.2012.12.106. Epub 2013 Jan 9.
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.
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.
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.
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.
我们之前建立了一种新型的人结直肠癌原代培养方法。该方法称为肿瘤组织来源的球体方法，涉及制备原代癌细胞的多细胞球体，使细胞间保持接触。我们将该方法应用于人膀胱癌。
按照用于人结直肠癌的相同方案，从异种移植或原发性人膀胱尿路上皮癌肿瘤中制备肿瘤组织来源的球体。使用免疫组织化学、Western blot 和聚合酶链反应对肿瘤组织来源的球体进行特征分析。
我们建立了一个原发性膀胱尿路上皮癌的异种移植，并从异种移植肿瘤中分离和培养了肿瘤组织来源的球体。肿瘤组织来源的球体保留了原始肿瘤和异种移植的特征。赫赛汀促进肿瘤组织来源的球体生长，PI3K 和 mTOR 的抑制剂以及拉帕替尼抑制赫赛汀诱导的生长，但厄洛替尼不抑制。我们还从原发性膀胱尿路上皮癌中制备了肿瘤组织来源的球体。非肌肉浸润性尿路上皮癌建立原发性癌症组织球体的成功率为 90.7%，肌肉浸润性癌症为 68.2%。总成功率为 84.2%。赫赛汀促进了 7 名患者中的 4 名的原发性癌症组织球体的生长。
我们报告了一种建立人膀胱癌细胞原代培养的方法。异种移植和原发性肿瘤中肿瘤组织来源的球体中赫赛汀的生长刺激表明针对人膀胱癌的 HER3 信号靶向治疗的可能性。肿瘤组织来源的球体方法可能有助于选择接受拉帕替尼等分子靶向药物的患者。
