Fibroblasts potentiate melanoma cells in vitro invasiveness induced by UV-irradiated keratinocytes
Fibroblasts potentiate melanoma cells in vitro invasiveness induced by UV-irradiated keratinocytes
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DOI：
10.1007/s00418-018-1650-4
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发表时间：
2018-05-01
影响因子：
2.3
通讯作者：
Lacina, Lukas
中科院分区：
文献类型：
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作者：
Jobe, Njainday Pulo;Zivicova, Veronika;Lacina, Lukas
黑色素瘤是一种发病率稳步上升的恶性疾病。紫外线照射是黑色素瘤发生的公认关键因素。因此，有效预防紫外线组织损伤对预防黑色素瘤具有重要的潜力。在这项研究中，我们测试了正常角质形成细胞的紫外线照射的效果，以及它们与从黑色素瘤中分离的正常和癌症相关成纤维细胞的相互作用。使用这个模型的紫外线影响的微环境，我们测量黑色素瘤细胞迁移的3-D胶原蛋白凝胶。这些相互作用进行了研究，使用DNA微阵列技术，免疫荧光染色，单细胞电泳分析，活力（死/活）细胞检测方法，和迁移分析。我们观察到，在72小时内以相等的间隔将三个10 mJ/cm（2）的组分应用于角质形成细胞，导致黑色素瘤细胞体外侵袭增加50%（p < 0.05）。将癌症相关的成纤维细胞引入这种模型进一步显著刺激黑素瘤细胞的体外侵袭性，其程度高于正常成纤维细胞。一组负责促进黑色素瘤细胞侵袭的候选基因产物被定义，重点是IL-6、IL-8和CXCL-1。总之，本研究表明，在体外条件下，癌症微环境和紫外线照射在黑色素瘤侵袭性中具有协同作用。
Melanoma represents a malignant disease with steadily increasing incidence. UV-irradiation is a recognized key factor in melanoma initiation. Therefore, the efficient prevention of UV tissue damage bears a critical potential for melanoma prevention. In this study, we tested the effect of UV irradiation of normal keratinocytes and their consequent interaction with normal and cancer-associated fibroblasts isolated from melanoma, respectively. Using this model of UV influenced microenvironment, we measured melanoma cell migration in 3-D collagen gels. These interactions were studied using DNA microarray technology, immunofluorescence staining, single cell electrophoresis assay, viability (dead/life) cell detection methods, and migration analysis. We observed that three 10 mJ/cm(2) fractions at equal intervals over 72 h applied on keratinocytes lead to a 50% increase (p < 0.05) in in vitro invasion of melanoma cells. The introduction cancer-associated fibroblasts to such model further significantly stimulated melanoma cells in vitro invasiveness to a higher extent than normal fibroblasts. A panel of candidate gene products responsible for facilitation of melanoma cells invasion was defined with emphasis on IL-6, IL-8, and CXCL-1. In conclusion, this study demonstrates a synergistic effect between cancer microenvironment and UV irradiation in melanoma invasiveness under in vitro condition.