IL-6 promotion of glioblastoma cell invasion and angiogenesis in U251 and T98G cell lines.
Interleukin-6 (IL-6) is a growth and survival factor in human glioblastoma cells and plays an important role in malignant progression. However, its role in glioblastoma invasion is still unknown. This study shows how IL-6 promotes cell invasion and migration in U251 and T98G glioblastoma cell lines. The underlying mechanism includes both protease-dependent and -independent manners. Stimulation with IL-6 increased MMP9 expression in the two cell lines but had no influence on MMP2 expression. Fascin-1 is a cell skeleton binding protein and plays a key role in cell migration and invasion. Its binding style directly influences cell morphology and tendency to become deformed. After IL-6 exposure, fascin-1 expression increased in an IL-6 dose-dependent manner. Immunofluorescence also revealed that the binding style of fascin-1 had changed after IL-6 exposure, resulting in a more invasive phenotype of the cells. Three most commonly emphasized invasion-associated signaling pathways, including JAK-STAT3, p42/44 MAPK, and PI3K/AKT, were verified to further illustrate its underlying mechanism. Only phosphorylation of STAT3 at ser 727 site paralleled the IL-6 stimulation, and JSI-124, a specific JAK-STAT3 pathway blocker, deterred the invasion and migration promotive effect of IL-6, indicating that the JAK/STAT3 pathway mediates signal transduction. Furthermore, IL-6 also acts in a paracrine fashion to promote vascular endothelial cell migration, thus facilitating tumor angiogenesis and invasion. These results suggest that IL-6 promotes glioblastoma cell invasion and angiogenesis and may be a potential anti-invasion target.
Liu
Qinglin
Q
Department of Neurosurgery, Qi Lu Hospital, Shandong University, Wenhua Xi Road, Jinan, Shandong, People's Republic of China.
Li
Gang
G
Li
Ronghui
R
Shen
Jie
J
He
Qiaowei
Q
Deng
Lin
L
Zhang
Cai
C
Zhang
Jian
J
D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D005455:Fluorescent Antibody Technique; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D015151:Immunoblotting; D015850:Interleukin-6 / Q000096:biosynthesis*; D008840:Microfilament Proteins / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology
D002352:Carrier Proteins; C502658:FSCN1 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D008840:Microfilament Proteins