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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Oncoimmunology
2016 ; 5
(10
): e1219828
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Peritumoral stromal neutrophils are essential for c-Met-elicited metastasis in
human hepatocellular carcinoma
#MMPMID27853643
He M
; Peng A
; Huang XZ
; Shi DC
; Wang JC
; Zhao Q
; Lin H
; Kuang DM
; Ke PF
; Lao XM
Oncoimmunology
2016[]; 5
(10
): e1219828
PMID27853643
show ga
Inflammation is a component of tumor progression mechanisms. Neutrophils are a
common inflammatory infiltrate in many tumors, but their regulation and functions
in neoplasia are not understood. Here, we showed, in detailed studies of c-Met
molecule in 225 untreated patients with hepatocellular carcinoma (HCC), that high
infiltration of neutrophils in HCC tissues determined malignant cell
c-Met-associated clinical outcome of patients. High infiltration of neutrophils
in HCCs determined malignant cell c-Met-associated clinical outcome of patients.
Neutrophils were enriched predominantly in invading tumor edge of HCCs; the
accumulated neutrophils were the major source of c-Met ligand HGF in HCCs.
Exposure to HCC environments resulted in neutrophil activation and the following
HGF production. Inhibiting the activities of Erk1/2, p38, and NF-?B, but not the
phosphorylation of AKT or JNK, successfully attenuated the neutrophil HGF
production induced by HCC environments. Further investigation revealed that
GM-CSF was an important determinant in malignant cell-elicited neutrophil HGF
production in vitro and in vivo. Moreover, we demonstrated that tumor
neutrophils, via HGF/c-Met interaction, actively enhanced the metastasis of
malignant cells in vitro and in vivo. These data provide direct evidence
supporting the critical role of neutrophils in human tumor progression and reveal
a fine-tuned collaborative action between cancer cells and immune cells in tumor
milieu, which reroutes the immune activation into a tumor-promoting direction.