Involvement of Heregulin/HER3 in the Primary Culture of Human Urothelial Cancer

No AccessJournal of UrologyInvestigative Urology1 Jul 2013Involvement of Heregulin/HER3 in the Primary Culture of Human Urothelial Cancer Hiroaki Okuyama, Takahiro Yoshida, Hiroko Endo, Masashi Nakayama, Norio Nonomura, Kazuo Nishimura, and Masahiro Inoue Hiroaki OkuyamaHiroaki Okuyama Department of Pathology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan More articles by this author , Takahiro YoshidaTakahiro Yoshida Department of Biochemistry, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan More articles by this author , Hiroko EndoHiroko Endo Department of Biochemistry, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan More articles by this author , Masashi NakayamaMasashi Nakayama Department of Urology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan More articles by this author , Norio NonomuraNorio Nonomura Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan More articles by this author , Kazuo NishimuraKazuo Nishimura Department of Urology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan More articles by this author , and Masahiro InoueMasahiro Inoue Department of Biochemistry, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan Department of Clinical and Experimental Pathophysiology, Osaka University, Graduate School of Pharmaceutical Sciences, Suita, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.12.106AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract 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. 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Google Scholar © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited byAtala A (2019) Re: Mouse and Human Urothelial Cancer Organoids: A Tool for Bladder Cancer ResearchJournal of Urology, VOL. 202, NO. 4, (664-664), Online publication date: 1-Oct-2019. Volume 190Issue 1July 2013Page: 302-310Supplementary Materials Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.Keywordsurotheliumcarcinoma, transitional cellneuregulin-1primary cell cultureurinary bladderAcknowledgmentsAtsuko Mizukoshi, Momoko Shiozaki and Toshiko Yasuda provided technical assistance. Miyabi Izutu assisted with the manuscript.MetricsAuthor Information Hiroaki Okuyama Department of Pathology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan More articles by this author Takahiro Yoshida Department of Biochemistry, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan More articles by this author Hiroko Endo Department of Biochemistry, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan More articles by this author Masashi Nakayama Department of Urology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan More articles by this author Norio Nonomura Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan More articles by this author Kazuo Nishimura Department of Urology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan More articles by this author Masahiro Inoue Department of Biochemistry, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan Department of Clinical and Experimental Pathophysiology, Osaka University, Graduate School of Pharmaceutical Sciences, Suita, Japan More articles by this author Expand All Advertisement PDF downloadLoading ...