Dermatology Department, University Hospital, Zürich, Switzerland.
Pigment Cell Melanoma Res. 2012 Mar;25(2):275-8. doi: 10.1111/j.1755-148X.2011.00944.x. Epub 2012 Jan 6.
The incidence of melanoma has significantly increased, and a better understanding of its pathogenesis and development of new therapeutic strategies are urgently needed. Here, we describe a murine model of metastatic cutaneous melanoma using C57BL/6 mice expressing a mutated human N-Ras gene under the control of a tyrosinase promoter (TyrRas). These mice were topically exposed to 7,12- dimethylbenzanthracene (DMBA) for brief exposure periods. Cutaneous melanoma developed at the site of exposure on average by 19 weeks of age and in 80% of mice. Importantly, as in humans, melanoma development was associated with subsequent metastasis to tumor-draining lymph nodes. Critically, such metastatic behavior is transplantable, as intradermal inoculation of melanoma cells from TyrRas-DMBA mice into non-transgenic mice led to the growth of melanoma and, again, metastasis to skin-draining lymph nodes. This metastatic melanoma model closely mimics human pathology and should be a useful tool for studying melanoma pathogenesis and developing new therapies.
黑色素瘤的发病率显著增加，因此迫切需要更好地了解其发病机制和开发新的治疗策略。在这里，我们描述了一种使用 C57BL/6 小鼠的转移性皮肤黑色素瘤模型，这些小鼠表达受酪氨酸酶启动子（TyrRas）控制的突变型人 N-Ras 基因。这些小鼠被局部暴露于 7,12-二甲基苯并蒽（DMBA）中进行短暂暴露。皮肤黑色素瘤在暴露部位的平均出现时间为 19 周龄，在 80%的小鼠中出现。重要的是，与人类一样，黑色素瘤的发展与随后的肿瘤引流淋巴结转移有关。关键的是，这种转移性行为是可移植的，因为将 TyrRas-DMBA 小鼠的黑色素瘤细胞皮内接种到非转基因小鼠中会导致黑色素瘤的生长，并再次导致皮肤引流淋巴结的转移。这种转移性黑色素瘤模型非常类似于人类病理学，应该是研究黑色素瘤发病机制和开发新疗法的有用工具。
