Phosphoglucose isomerase/autocrine motility factor promotes melanoma cell migration through ERK activation dependent on autocrine production of interleukin-8.
It is well known that phosphoglucose isomerase/autocrine motility factor (AMF) promotes cell migration in an autocrine manner in various tumor cells. However, it remains unclear whether certain cytokines modulate the effects of AMF on tumor cell migration. Because interleukin (IL)-8, a proinflammatory cytokine, is produced by melanoma cells and has been correlated with melanoma migration, the migratory ability of melanoma cells induced by AMF may also involve induction of IL-8 expression. In the present study, we assessed whether AMF promotes melanoma cell migration through autocrine production of IL-8. We found that AMF stimulation increased IL-8 production through up-regulation of IL-8 mRNA transcription, especially in biologically early stage melanoma cells. AMF-induced migration of these cells was inhibited by a specific neutralizing antibody against IL-8. The IL-8 production induced by AMF was mediated by the ERK1/2 pathways. These findings suggest that melanoma migration induced by AMF is mediated by autocrine production of IL-8 as a novel downstream modulator of the AMF signaling pathway.
Araki
Kenichiro
K
Department of General Surgical Science (Surgery I), Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, Japan. karaki@showa.gunma-u.ac.jp
Shimura
Tatsuo
T
Yajima
Toshiki
T
Tsutsumi
Soichi
S
Suzuki
Hideki
H
Okada
Kohji
K
Kobayashi
Tsutomu
T
Raz
Avraham
A
Kuwano
Hiroyuki
H
D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D005956:Glucose-6-Phosphate Isomerase / Q000378:metabolism*; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D008954:Models, Biological; D010766:Phosphorylation; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D016209:Interleukin-8; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D005956:Glucose-6-Phosphate Isomerase