IL-6 augments the invasiveness of U87MG human glioblastoma multiforme cells via up-regulation of MMP-2 and fascin-1.
Invasion into adjacent brain parenchyma is the key cause of recurrent human glioblastoma multiforme (GBM). The role of interleukin 6 (IL-6) in the malignant progression of glioma remains undefined. Here, we found that IL-6 promotes the invasion of U87 MG human glioma cells but not in U343 cells. An advanced level of STAT3 activity, and increased expression and secretion of MMP-2, induced by IL-6 in U87 MG cells were observed. Blocking the STAT3 pathway with specific inhibitors of STAT3, JSI-124 or small interfering RNA (siRNA), inhibited the invasion of U87MG promoted by IL-6 with concomitant down-regulation of MMP-2. Furthermore, rapid up-regulation of fascin-1 (a cell motility-related protein) induced by IL-6 was apparent in U87MG cells. However, this up-regulation of fascin-1 was not inhibited by JSI-124 or siRNA. These results suggest that the STAT3 pathway and fascin-1 may play crucial roles in the invasiveness of U87MG cells promoted by IL-6.
Li
Ronghui
R
Department of Neurosurgery, Qilu Hospital, Shandong University, Jinan, PR China.
Li
Gang
G
Deng
Lin
L
Liu
Qinglin
Q
Dai
Jun
J
Shen
Jie
J
Zhang
Jian
J
D015153:Blotting, Western; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D008840:Microfilament Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D002352:Carrier Proteins; C502658:FSCN1 protein, human; D015850:Interleukin-6; D008840:Microfilament Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D020778:Matrix Metalloproteinase 2