Ultraviolet-B irradiation enhances melanoma cell motility via induction of autocrine interleukin 8 secretion.
Ultraviolet radiation (UVR) is known to be involved in the initiation and progression of malignant melanoma. Many studies have focused on the initiation of melanoma, but less is known about the effect of UVR on established tumor cells. Here, we show that after ultraviolet-B (UVB) irradiation, melanoma cells (MM) are able to secrete autocrine factors that enhance their motility. Time-lapse videomicroscopy of UVB irradiated (15 or 30 mJ/cm(2)) MM showed an initial decrease in MM cell motility one hour after irradiation, with subsequent increase 24 h after UV-B treatment. Conditioned media harvested from MM 24 h following UV-B irradiation specifically enhanced the motility of un-irradiated MM, suggesting that a newly synthesized soluble factor released by UVB MM is involved. As interleukin 8 (IL-8) is known to be up-regulated by different cell types after UV-B irradiation, we investigated IL-8 expression after UVB exposure. Quantitative RT-PCR and ELISA demonstrated an induction of IL-8 in MM by UVB (15 or 30 mJ/cm(2)), and addition of recombinant IL-8 to cell cultures enhanced cell motility to a similar degree than UVB. Importantly, blocking IL-8 activity by a neutralizing anti IL-8 antibody inhibited the up-regulation of MM motility after UVB treatment. We conclude that UVB enhances MM motility and that this effect is mediated at least in part by IL-8 released by MM in an autocrine fashion. Our findings are consistent with the hypothesis that UVB is not only involved in the initiation of melanoma, but may also be important for some aspects of tumor progression.
Gebhardt
Carl
C
Department of Dermatology, Venerology and Allergology, University of Leipzig, Leipzig, Germany. carl.gebhardt@medizin.uni-leipzig.de
Averbeck
Marco
M
Viertel
Andrea
A
Kauer
Friederike
F
Saalbach
Anja
A
Anderegg
Ulf
U
Simon
Jan C
JC
D008841:Actin Cytoskeleton / Q000378:metabolism / Q000528:radiation effects; D000199:Actins / Q000378:metabolism; D000906:Antibodies / Q000494:pharmacology; D019898:Autocrine Communication / Q000276:immunology / Q000528:radiation effects*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000276:immunology / Q000528:radiation effects*; D015870:Gene Expression / Q000276:immunology / Q000528:radiation effects; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008545:Melanoma / Q000276:immunology / Q000556:secondary*; D012333:RNA, Messenger / Q000378:metabolism; D012878:Skin Neoplasms / Q000276:immunology / Q000473:pathology*; D012995:Solubility; D014466:Ultraviolet Rays
D000199:Actins; D000906:Antibodies; D016209:Interleukin-8; D012333:RNA, Messenger