2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces matrix metalloproteinase (MMP) expression and invasion in A2058 melanoma cells
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces matrix metalloproteinase (MMP) expression and invasion in A2058 melanoma cells
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DOI：
10.1016/j.taap.2005.05.001
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发表时间：
2006-02-01
影响因子：
3.8
通讯作者：
White, LA
中科院分区：
文献类型：
--
作者：
Villano, CM;Murphy, KA;White, LA
从1973年到1992年，美国黑色素瘤相关死亡率增加了34%。虽然目前对恶性黑色素瘤的成功治疗很少，但已知遗传易感性和环境因素有助于黑色素瘤的发生和进展。过度的紫外线暴露被认为是黑色素瘤发生的主要病因，然而，流行病学和实验证据表明，暴露于环境致癌物有助于黑色素瘤。我们提出，暴露于环境中的化学物质，激活芳香烃受体途径有助于黑色素瘤的进展，特别是通过刺激基质金属蛋白酶（MMPs）的表达和活性。因此，我们研究了AhR激活对正常人巨细胞和几种黑色素瘤细胞系的影响。本文提供的数据表明，正常黑素细胞和黑色素瘤细胞表达AhR和Arm：，并且对TCDD的激活有反应。此外，在转化的黑素瘤细胞（A2058）中激活该途径导致MMP-1、MMP-2和MMP-9的表达和活性增加，以及使用体外侵袭测定增加的侵袭。此外，TCDD诱导的MMP-1启动子在黑色素瘤细胞中的表达似乎需要不同的元素比那些需要在未转化的细胞，这表明该途径可能有多种机制激活MMP的表达。(c)2005年爱思唯尔公司All rights reserved.
There has been a 34% increase in melanoma related mortality in the United States from 1973 to 1992. Although few successful treatments for malignant melanoma exist, it is known that genetic susceptibility and environmental factors contribute to the initiation and progression of melanoma. Excessive UV exposure is considered the main etiological factor in melanoma initiation, however, epidemiological and experimental evidence suggests that exposure to environmental carcinogens contribute to melanoma. We propose that exposure to environmental chemicals that activate the aryl hydrocarbon receptor pathway contribute to melanoma progression, specifically through stimulation of the expression and activity of the matrix metalloproteinases (MMPs). Therefore, we investigated the effect of AhR activation on normal human metanocytes and several melanoma cell lines. The data presented here demonstrate that normal melanocytes and melanoma cells express the AhR and Arm: and are responsive to activation by TCDD. Furthermore, activation of this pathway in transformed melanoma cells (A2058) results in increased expression and activity of MMP-1, MMP-2 and MMP-9, as well as increased invasion using in vitro invasion assays. Furthermore, TCDD-induced expression of the MMP-1 promoter in melanoma cells appears to require different elements than those required in untransformed cells, indicating that this pathway may have multiple mechanisms for activation of MMP expression. (c) 2005 Elsevier Inc. All rights reserved.