Bar-Eli M
Department of Cell Biology, The University of Texas M.D. Anderson Cancer Center, Houston, Tex. 77030, USA.
Pathobiology. 1999;67(1):12-8. doi: 10.1159/000028045.
Expression of 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 role 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 the IL-8 gene rendered them highly tumorigenic and increased their metastatic potential in nude mice. The IL-8-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.
人黑色素瘤细胞中白细胞介素 -8（IL-8）的表达与其在体内的转移潜能相关。此外，原发性皮肤黑色素瘤的紫外线B（UVB）照射可诱导IL-8信使核糖核酸（mRNA）和蛋白质的产生，并增加裸鼠体内肿瘤的生长和转移。尽管IL-8已被证明是一种血管生成因子，但黑色素瘤细胞中IL-8产生增加的生物学后果以及IL-8在转移过程中的作用仍不清楚。本综述的目的是确定IL-8在人黑色素瘤肿瘤生长和转移中的作用。用IL-8基因转染非转移性且IL-8阴性的黑色素瘤细胞，使其具有高度致瘤性，并增加其在裸鼠中的转移潜能。IL-8转染的细胞显示基质金属蛋白酶-2（MMP-2）表达和活性上调，并通过基质胶包被的滤膜增加侵袭性。IL-8对MMP-2的激活可增强肿瘤细胞对宿主基质的侵袭，并增加血管生成，从而促进转移。除UVB外，缺氧条件也可上调IL-8，这表明环境在调节IL-8表达和转移中起主要作用。本综述总结的研究表明，在黑色素瘤中，IL-8可能作为区分良性和恶性细胞的血管生成因子。
