Neutrophils enhance invasion activity of human cholangiocellular carcinoma and hepatocellular carcinoma cells: an in vitro study.
OBJECTIVE
Tumor-mesenchymal interactions are involved in the mechanism of tumor invasion in several types of carcinoma. Mutual interactions between carcinoma cells and neutrophils, however, have been poorly understood. In the present study we examined the effect of neutrophils on invasion activities of carcinoma cells in vitro. Role of hepatocyte growth factor (HGF) as a mediator was also evaluated.


METHODS
Using a Matrigel invasion chamber, invasion activities of HuCC-T1 human cholangiocellular carcinoma cells and HepG2 hepatocellular carcinoma cells in response to recombinant HGF or neutrophils were evaluated.


RESULTS
Recombinant HGF dose-dependently increased invasion activities of HuCC-T1 and HepG2 cells. Neutrophils significantly enhanced invasion activities of these cells, which were suppressed to the respective basal levels with anti-HGF antibody. The carcinoma cells did not secrete HGF. Neutrophils cultivated in tumor condition medium (TCM) of HuCC-T1 or HepG2 cells secreted a significant level of HGF protein without increasing HGF mRNA expression. Treatment with heat or ultrafiltration of TCM of HuCC-T1 or HepG2 cells suggested carcinoma cell-derived HGF inducer(s) to be certain protein(s) with a molecular weight of more than 30 000.


CONCLUSIONS
The present study suggests the presence of mutual interactions between HuCC-T1/HepG2 carcinoma cells and neutrophils in tumor invasion via paracrine regulation mediated by neutrophil-derived HGF.
Imai
Yoshihito
Y
The Third Department of Internal Medicine, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi, Osaka 570-8506, Japan. imaiy@takii.kmu.ac.jp
Kubota
Yoshitsugu
Y
Yamamoto
Shin
S
Tsuji
Kazuyuki
K
Shimatani
Masaaki
M
Shibatani
Nobuyuki
N
Takamido
Shoichiroh
S
Matsushita
Masanori
M
Okazaki
Kazuichi
K
D001650:Bile Duct Neoplasms / Q000473:pathology / Q000503:physiopathology; D001653:Bile Ducts, Intrahepatic / Q000473:pathology; D015152:Blotting, Northern; D006528:Carcinoma, Hepatocellular / Q000473:pathology* / Q000503:physiopathology; D018281:Cholangiocarcinoma / Q000473:pathology* / Q000503:physiopathology; D004797:Enzyme-Linked Immunosorbent Assay; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008113:Liver Neoplasms / Q000473:pathology* / Q000503:physiopathology; D009361:Neoplasm Invasiveness / Q000473:pathology; D009504:Neutrophils / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D017228:Hepatocyte Growth Factor