title: Establishment and characterization of novel gastric signet-ring cell and non signet-ring cell poorly differentiated adenocarcinoma cell lines with low and high malignant potential.
abstract: BACKGROUND
  Poorly differentiated signet-ring cell carcinoma (SRCC) and non signet-ring cell carcinoma (NSRCC) are prevalent histological subtypes of gastric cancers with distinct morphological features. To date, however, the molecular basis of their growth, differentiation, and metastasis still remains unclear, because of the limitation of available cell lines.
  
  
  METHODS
  In the present study, we established novel SRCC and NSRCC cell lines (designated GPM-2 and GPM-1) derived from the ascites of two individual gastric cancer patients with peritoneal metastasis.
  
  
  RESULTS
  Immunohistochemical and quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis revealed that GPM-2 cells showed both gastric and intestinal differentiation phenotypes (E-cadherin+/MUC5AC+/MUC6+/Villin+), and formed xenografted tumors with typical SRCC histology in nude mice. In contrast, GPM-1 cells only weakly expressed differentiation markers, showing a phenotype of E-cadherin(low)+/MUC2-/MUC5AC-/Villin(low)+. Characteristically, GPM-2 cells were found to highly express both membrane-bound mucin (MUC1/MUC4) and secreted mucin glycoproteins (MUC5AC/MUC6), whose expression is regulated by an epigenetic mechanism such as histone acetylation. GPM-2 cells also secreted a large amount of sTn antigen into the culture medium. These mucin profiles of GPM-2 cells are distinct from those of conventional SRCC cell lines (KATO III and HSC-39), which preferentially express intestinal MUC2/MUC4 as well as sLe(x) and sLe(A) antigens. In addition, GPM-2 cells showed a slow growth rate, and a lower metastatic potential than GPM-1 cells.
  
  
  CONCLUSIONS
  These results indicate that the cells of the new SRCC line, GPM-2 cells, are more differentiated and less aggressive than NSRCC-type GPM-1 cells, and would thus offer an excellent model for understanding the molecular mechanism underlying the growth, differentiation, and mucin production of an SRCC gastric cancer cell line.
authors.affiliation: Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Murakami
authors.forename: Hayao
authors.initials: H
authors.lastname: Nakanishi
authors.forename: Harunari
authors.initials: H
authors.lastname: Tanaka
authors.forename: Seiji
authors.initials: S
authors.lastname: Ito
authors.forename: Kazunari
authors.initials: K
authors.lastname: Misawa
authors.forename: Yuuichi
authors.initials: Y
authors.lastname: Ito
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Ikehara
authors.forename: Eisaku
authors.initials: E
authors.lastname: Kondo
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kodera
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology*; D000328:Adult; D000818:Animals; D001201:Ascites / Q000209:etiology / Q000473:pathology; D018279:Carcinoma, Signet Ring Cell / Q000473:pathology*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation / Q000379:methods; D010534:Peritoneal Neoplasms / Q000473:pathology* / Q000556:secondary; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000473:pathology*