Gene expression screening using a cDNA macroarray to clarify the mechanisms of peritoneal dissemination of pancreatic cancer.
OBJECTIVE
Pancreatic cancer is associated with the poorest prognosis of any digestive cancer due to the high incidence of peritoneal dissemination, which is the cause of death in most cases. To determine the mechanisms of peritoneal dissemination in pancreatic cancer, we established a mouse model of high peritoneal dissemination.


METHODS
A novel highly peritoneal-disseminating cell line was established from the human pancreatic cancer cell line; CAPAN-1. The new cell line, CAPAN-1P4a, was established from CAPAN-1 by repeated in vivo selection (four times) of the tumor cell line. To clarify the candidate genes implicated in peritoneal dissemination of pancreatic cancer, global gene expression screening was done using a cDNA macroarray.


RESULTS
CAPAN-1P4a cells showed 100% metastasis 3 weeks after injection and high reproducibility in the inoculated mice. Twenty-seven genes were upregulated and 14 genes were downregulated in CAPAN-1P4a cells compared with CAPAN-1 cells. The genes differentially expressed in the two cell lines were included as tumor suppressor/apoptosis genes, regulatory transcription factor, membrane receptors, cell adhesion protein, membrane receptors, and so on.


CONCLUSIONS
Our established CAPAN-1P4a model offers a new means of conducting global gene expression analysis of pancreatic cancer cells with peritoneal dissemination and it has the potential to provide new insights into the mechanism of peritoneal dissemination in human pancreatic cancer.
Nakajima
Futoshi
F
Department of Surgery 1, Sapporo Medical University School of Medicine, Chuo-ku, Japan.
Nishimori
Hidefumi
H
Hata
Fumitake
F
Yasoshima
Takahiro
T
Nomura
Hiroki
H
Tanaka
Hiroshi
H
Ohno
Keisuke
K
Yanai
Yoshiyuki
Y
Kamiguchi
Kenjiro
K
Sato
Noriyuki
N
Denno
Ryuichi
R
Hirata
Koichi
K
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D000818:Animals; D002460:Cell Line; D018076:DNA, Complementary; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000473:pathology*; D010534:Peritoneal Neoplasms / Q000556:secondary; D014407:Tumor Cells, Cultured / Q000473:pathology
D018076:DNA, Complementary