Development and Characterization of a Novel in vitro Progression Model for UVB-Induced Skin Carcinogenesis.
Development and Characterization of a Novel in vitro Progression Model for UVB-Induced Skin Carcinogenesis.
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DOI：
10.1038/srep13894
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发表时间：
2015-09-09
影响因子：
4.6
通讯作者：
Singh S
中科院分区：
文献类型：
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作者：
Tyagi N;Bhardwaj A;Srivastava SK;Arora S;Marimuthu S;Deshmukh SK;Singh AP;Carter JE;Singh S
流行病学研究表明，阳光中的紫外线B（UVB）成分（290-320 nm）是皮肤癌发生的最普遍病因-仅在美国，每年就有超过200万例新发病例。UVB诱发皮肤癌的发生是一个多步骤的复杂过程。UVB诱导的皮肤癌发生过程中发生的分子事件知之甚少，主要是由于缺乏适当的细胞模型系统。因此，为了在这一领域取得进展，我们已经开发了一种体外模型，UVB诱导的皮肤癌，通过反复暴露于UVB辐射使用永生化的人表皮角质形成细胞（HaCaT）细胞。我们表明，UVB转化HaCaT细胞获得增强的增殖率，抗肿瘤，并在一个渐进的方式集落和球体形成的能力。此外，这些细胞表现出增加的侵袭性，具有增强的迁移和侵袭潜力以及间充质表型。此外，这些衍生的细胞在接种到裸鼠中后能够形成侵袭性鳞状细胞癌，而亲本HaCaT细胞保持非致瘤性。总之，这些新的，UVB转化的进展模型细胞系可以非常有助于获得有价值的机制深入了解UVB诱导的皮肤癌变，识别新的分子靶点的诊断和治疗意义，并在体外筛选新的预防和治疗药物。
Epidemiological studies suggest ultraviolet B (UVB) component (290–320 nm) of sun light is the most prevalent etiologic factor for skin carcinogenesis- a disease accounting for more than two million new cases each year in the USA alone. Development of UVB-induced skin carcinoma is a multistep and complex process. The molecular events that occur during UVB-induced skin carcinogenesis are poorly understood largely due to the lack of an appropriate cellular model system. Therefore, to make a progress in this area, we have developed an in vitro model for UVB-induced skin cancer using immortalized human epidermal keratinocyte (HaCaT) cells through repetitive exposure to UVB radiation. We demonstrate that UVB-transformed HaCaT cells gain enhanced proliferation rate, apoptosis-resistance, and colony- and sphere-forming abilities in a progressive manner. Moreover, these cells exhibit increased aggressiveness with enhanced migration and invasive potential and mesenchymal phenotypes. Furthermore, these derived cells are able to form aggressive squamous cell carcinoma upon inoculation into the nude mice, while parental HaCaT cells remain non-tumorigenic. Together, these novel, UVB-transformed progression model cell lines can be very helpful in gaining valuable mechanistic insight into UVB-induced skin carcinogenesis, identification of novel molecular targets of diagnostic and therapeutic significance, and in vitro screening for novel preventive and therapeutic agents.