Establishment and biological characterization of a novel cell line derived from hepatoid adenocarcinoma originated at the ampulla of Vater.
Hepatoid adenocarcinoma is a rare gastrointestinal tumor and mostly reported in the stomach. Effective chemotherapy has yet to be developed to improve poor prognosis. The present study was undertaken to establish a useful cell line derived from a hepatoid adenocarcinoma, possibly leading to a new therapeutic strategy. The new human cell line VAT-39 was established from a metastatic lymph node of a 69-year-old Japanese male patient with hepatoid adenocarcinoma of the ampulla of Vater. The primary tumor and metastatic lymph node were composed of hepatoid adenocarcinoma cells exhibiting immunohistochemical reactivity for alpha-fetoprotein (AFP) and glypican-3 (GPC3). In the metastatic lymph node, Periodic acid-Schiff (PAS) staining clarified diffuse deposition of glycogen in the cytoplasm, indicating analogous characteristics to the primary hepatoid adenocarcinoma. Moreover, VAT-39 cells produced high levels of AFP in the cultured medium, and reverse-transcriptase polymerase chain reaction (RT-PCR) verified increased expression of GPC3 mRNA in this cell line. Further, we evaluated the sensitivity to major chemotherapeutic drugs against the bile duct cancer. Neither 5-fluorouracil nor gemcitabine showed particular sensitivity to this cell line. The tumorigenicity of the cultured cells was confirmed in athymic nude mice and the histological features of the explanted tumor were similar to the VAT-39 cell line. The present VAT-39 is the first hepatoid adenocarcinoma cell line that originates from the ampulla of Vater and it will be applicable for basic biological studies searching for new strategies of molecular targeted chemotherapy to this disease.
Department of Anatomy, Ultrastructural Cell Biology, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki 889-1692, Japan.
Nobuyasu
N
Takahashi
Department of Anatomy, Ultrastructural Cell Biology, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki 889-1692, Japan.
Fumiyo
F
Aoyama
Department of Surgical Oncology and Regulation of Organ Function, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki 889-1692, Japan.
Masahide
M
Hiyoshi
Section of Oncopathology and Regenerative Biology, Department of Pathology, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki 889-1692, Japan.
Hiroaki
H
Kataoka
Department of Anatomy, Ultrastructural Cell Biology, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki 889-1692, Japan.
Akira
A
Sawaguchi
D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology*; D000368:Aged; D014670:Ampulla of Vater / Q000166:cytology / Q000473:pathology*; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D001650:Bile Duct Neoplasms / Q000188:drug therapy / Q000473:pathology*; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D005472:Fluorouracil / Q000494:pharmacology; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy / Q000473:pathology*; D006003:Glycogen / Q000378:metabolism; D053673:Glypicans / Q000235:genetics / Q000276:immunology; D006801:Humans; D008198:Lymph Nodes / Q000166:cytology / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D012333:RNA, Messenger / Q000096:biosynthesis; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D000509:alpha-Fetoproteins / Q000096:biosynthesis / Q000276:immunology; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; C105937:GPC3 protein, human; D053673:Glypicans; D012333:RNA, Messenger; D000509:alpha-Fetoproteins; D003841:Deoxycytidine; D006003:Glycogen; D005472:Fluorouracil; D000093542:Gemcitabine