Ultraviolet‐B irradiation enhances melanoma cell motility via induction of autocrine interleukin 8 secretion

Abstract

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.

Role of TGF-β in Melanoma

“…In turn, neutrophils increase the migration and adhesion of human melanoma cells [78]. Furthermore, IL-8 can also stimulate the production of MMP like MMP9 and can increase melanoma cell motility [79,80].…”

CXCL8 and Its Cognate Receptors in Melanoma Progression and Metastasis

“…The expression of CXCL8, as well as its receptors CXCR1 and CXCR2, in melanoma has demonstrated a positive correlation with disease progression [14,15]. Ultraviolet-B radiation was also demonstrated to stimulate the production of CXCL8, which, in turn, enhanced the migration of metastatic melanoma cells in vitro [16]. Overexpression of CXCR1 and CXCR2 in melanoma cells confers the aggressive phenotypes on melanoma cells based on enhanced proliferation, migration and tumor growth in mice [13].…”

Low Molecular Weight Hyaluronan-Pulsed Human Dendritic Cells Showed Increased Migration Capacity and Induced Resistance to Tumor Chemoattraction

“…evidenced that IL-8 affects DC migratory capacity by increasing MMP-2 expression [64]. In addition, IL-8 acts in an autocrine and paracrine fashion on melanoma cells causing their enhanced migratory capacity [65]. Furthermore, it was described that pre-exposure to IL-8 results in desensitization of the DC to the chemotactic effects of IL-8.…”