Expression of interleukin-8 by human melanoma cells up-regulates MMP-2 activity and increases tumor growth and metastasis.
Expression of interleukin-8 by human melanoma cells up-regulates MMP-2 activity and increases tumor growth and metastasis.
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发表时间：
1997-10
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通讯作者：
M. Luca;Suyun Huang;J. Gershenwald;Rakesh K. Singh;R. Reich;M. Bar‐eli
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作者：
M. Luca;Suyun Huang;J. Gershenwald;Rakesh K. Singh;R. Reich;M. Bar‐eli
人黑色素瘤细胞表达白细胞介素-8（IL-8）与其转移潜能相关。此外，原代皮肤黑色素瘤细胞的UV-B照射诱导IL-8 mRNA和蛋白质的产生，并增加裸鼠肿瘤的生长和转移。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IL-8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。本研究的目的是确定IL-8在人黑色素瘤细胞的肿瘤生长和转移中的作用。用IL-8 cDNA转染IL-8水平可忽略不计的非转移性SB-2黑色素瘤细胞，随后分析其致瘤性和转移潜力的变化。与亲本和对照转染细胞相比，IL-8的强制表达使黑素瘤细胞高度致瘤性并增加其转移潜能。IL-8转染的细胞显示M（r）72，000 IV型胶原酶（MMP-2）mRNA和胶原酶活性上调，并通过Matrigel包被的过滤器增加侵袭力。此外，当MMP-2启动子连接氯霉素乙酰转移酶（CAT）报告基因的上游，CAT活性上调IL-8，但在对照转染细胞，表明IL-8参与MMP-2基因转录。IL-8激活IV型胶原酶可增强肿瘤细胞对宿主间质的侵袭，并增加血管生成，从而增加转移。
Expression of interleukin-8 (IL-8) by human melanoma cells correlates with their metastatic potential. Moreover, UV-B irradiation of primary cutaneous melanoma cells 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 study was to determine the role of IL-8 in tumor growth and metastasis of human melanoma cells. Nonmetastatic SB-2 melanoma cells with negligible levels of IL-8 were transfected with IL-8 cDNA and subsequently analyzed for changes in their tumorigenic and metastatic potential. Enforced expression of IL-8 rendered the melanoma cells highly tumorigenic and increased their metastatic potential as compared with parental and control transfected cells. The IL-8-transfected cells displayed up-regulation in M(r) 72,000 collagenase type IV (MMP-2) mRNA and collagenase activity and increased invasiveness through Matrigel-coated filters. Moreover, when the MMP-2 promoter was linked upstream of the chloramphenicol acetyltransferase (CAT) reporter gene, CAT activity was up-regulated in IL-8 but not in control transfected cells, suggesting that IL-8 is involved in MMP-2 gene transcription. Activation of type IV collagenase by IL-8 can enhance the invasion of host stroma by the tumor cells and increase angiogenesis and, hence, metastasis.