Role of interleukin-8 in tumor growth and metastasis of human melanoma

Role of interleukin-8 in tumor growth and metastasis of human melanoma
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DOI:
10.1159/000028045
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发表时间:
1999-01-01
期刊:
影响因子:
5
通讯作者:
Bar-Eli, M
Bar-Eli, M
中科院分区:
医学4区
文献类型:
--
作者:
Bar-Eli, M

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人黑色素瘤细胞表达IL-8与体内转移潜能相关。此外,UVB照射皮肤原发黑色素瘤可诱导IL-8mRNA和蛋白的产生,增加裸鼠体内肿瘤的生长和转移。虽然IL-8已被证明是一种血管生成因子,但黑色素瘤细胞产生的IL-8增加以及IL-8在转移过程中的作用的生物学后果尚不清楚。本综述的目的是确定IL-8在黑色素瘤生长和转移中的作用。将IL-8基因导入非转移性和IL-8阴性的黑色素瘤细胞,使其在裸鼠体内具有高度的致瘤性并增加其转移潜能。通过Matrigel包被的滤膜,IL8基因转染的细胞表现出基质金属蛋白酶-2表达和活性上调,侵袭力增强。IL-8激活基质金属蛋白酶-2可以增强肿瘤细胞对宿主间质的侵袭,增加血管生成,从而促进转移。除UVB外,低氧条件也可上调IL-8的表达,提示环境在调节IL-8的表达和转移中起重要作用。本文综述的研究表明,在黑色素瘤中,IL-8可能是区分良恶性细胞的血管生成因子。
Expressing interleukin-8 (IL-8) by human melanoma cells correlates with their metastatic potential in vivo. Moreover, UVB irradiation of primary cutaneous melanoma induces IL-8 mRNA and protein production and increases both tumor growth and metastasis in nude mice. Although IL-8 has been shown to be an angiogenic factor, the biological consequences of increased IL-8 production by melanoma cells and the ro le of IL-8 in the metastatic process remains unclear. The purpose of this review is to determine the role of IL-8 in tumor growth and metastasis of human melanoma. Transfection of nonmetastatic and IL-8-negative melanoma cells with IL-8 gene rendered them highly tumorigenic and increased their metastatic potential in nude mice. The IL8-transfected cells displayed upregulation of MMP-2 expression and activity and increased invasiveness through Matrigel-coated filters. Activation of MMP-2 by IL-8 can enhance the invasion of host stroma by the tumor cells and increase angiogenesis and, hence, metastasis, In addition to UVB, IL-8 can also be upregulated by hypoxia conditions, suggesting that the environment plays a major role in regulating IL-8 expression and metastasis, The studies summarized in this review suggest that in melanoma, IL-8 may serve as the angiogenic factor distinguishing benign from malignant cells.