title: Involvement of heregulin/HER3 in the primary culture of human urothelial cancer.
abstract: OBJECTIVE
  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.
  
  
  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.
authors: Department of Pathology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
authors: Hiroaki
authors: H
authors: Okuyama
authors: Takahiro
authors: T
authors: Yoshida
authors: Hiroko
authors: H
authors: Endo
authors: Masashi
authors: M
authors: Nakayama
authors: Norio
authors: N
authors: Nonomura
authors: Kazuo
authors: K
authors: Nishimura
authors: Masahiro
authors: M
authors: Inoue
mesh_terms: D015153:Blotting, Western; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy / Q000473:pathology*; D049109:Cell Proliferation; D006801:Humans; D007150:Immunohistochemistry; D058990:Molecular Targeted Therapy; D020890:Neuregulin-1 / Q000494:pharmacology*; D016133:Polymerase Chain Reaction / Q000379:methods; D020893:Receptor, ErbB-3 / Q000235:genetics / Q000378:metabolism*; D012680:Sensitivity and Specificity; D015398:Signal Transduction; D018874:Spheroids, Cellular / Q000187:drug effects; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured / Q000187:drug effects*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000473:pathology*
chemical_list: D020890:Neuregulin-1; C581292:ERBB3 protein, human; D020893:Receptor, ErbB-3