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.
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
Kenichiro
K
Araki
Tatsuo
T
Shimura
Toshiki
T
Yajima
Soichi
S
Tsutsumi
Hideki
H
Suzuki
Kohji
K
Okada
Tsutomu
T
Kobayashi
Avraham
A
Raz
Hiroyuki
H
Kuwano
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