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

Ultraviolet-B irradiation enhances melanoma cell motility via induction of autocrine interleukin 8 secretion
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DOI:
10.1111/j.1600-0625.2007.00572.x
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发表时间:
2007-08-01
影响因子:
3.6
通讯作者:
Simon, Jan C.
Simon, Jan C.
中科院分区:
医学2区
文献类型:
--
作者:
Gebhardt, Carl;Averbeck, Marco;Simon, Jan C.

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已知紫外线辐射(UVR)参与恶性黑色素瘤的发生和发展。许多研究都集中在黑色素瘤的发生上,但对UVR对已建立的肿瘤细胞的影响知之甚少。在这里,我们表明,紫外线-B(UVB)照射后,黑色素瘤细胞(MM)能够分泌自分泌因子,增强其运动性。UVB照射(15或30 mJ/cm(2))MM的延时视频显微镜显示,照射后1小时MM细胞运动性开始下降,随后在UV-B处理后24小时增加。条件培养基收获的MM 24小时后,UV-B照射,特别是增强运动的未照射MM,这表明一个新合成的可溶性因子释放的UVB MM参与。由于白细胞介素8(IL-8)是已知的上调不同类型的细胞照射后,UVB照射后,我们调查IL-8的表达。定量RT-PCR和ELISA证实UVB(15或30 mJ/cm(2))可诱导MM中的IL-8,向细胞培养物中加入重组IL-8可增强细胞运动性,其程度与UVB相似。重要的是,通过中和抗IL-8抗体阻断IL-8活性抑制UVB治疗后MM运动性的上调。我们的结论是,UVB增强MM的运动性,这种效果至少部分介导的IL-8释放MM在自分泌的方式。我们的研究结果与UVB不仅参与黑色素瘤的发生,而且可能对肿瘤进展的某些方面也很重要的假设一致。
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.