TGF-beta1 down-regulates ICAM-1 expression and enhances liver metastasis of pancreatic cancer.
OBJECTIVE
In order to study the regulation of adhesion-molecule expression by cytokines, we have investigated the effect of transforming growth factor-beta1. (TGF-beta1) on the expression of intercellular adhesion molecule-1 (ICAM-1) in human pancreatic cancer cell lines.


METHODS
By using three pancreatic cancer cell lines, SW1990, CAPAN-2 and PANC-1, the effect of TGF-beta1 on expression of ICAM-1, cancer cell immunogenicity and liver metastasis were investigated.


RESULTS
Cell surface ICAM-1 expression by ELISA on three cell lines were all reduced significantly by following incubation with various concentrations of TGF-beta1 and down-regulation of ICAM-1 expression was also observed at the mRNA level. Corresponding to the down expression of ICAM-1, the adhesion of peripheral blood mononuclear lymphocytes (PBMLs) to cancer cells and cancer cell cytotoxicity during co-culture with PBMLs were remarkably decreased by treatment with TGF-beta1. Furthermore, enhanced liver metastatic potential by in vivo splenic injection was observed in CAPAN-2 cells pretreated with TGF-beta1.


CONCLUSIONS
Since decreased expression of ICAM-1 has been known to contribute to cancer cell escape from immunologic recognition and cytotoxicity by effector cells, the present results indicate that unknown function of TGF-beta1 in the tumor progression and metastasis of pancreatic cancer.
Sawada
T
T
Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan. m1355299@med.osaka-cu.ac.jp
Kimura
K
K
Nishihara
T
T
Onoda
N
N
Teraoka
H
H
Yamashita
Y
Y
Yamada
N
N
Yashiro
M
M
Ohira
M
M
Hirakawa
K
K
D000818:Animals; D015152:Blotting, Northern; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000556:secondary*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D014183:Transplantation, Heterologous
D053773:Transforming Growth Factor beta1; D018799:Intercellular Adhesion Molecule-1