DOI：10.1038/nature17392 作者：Ashani T. Weeraratna
摘要 : 癌症的发病率随年龄增长而增加，这使得Ashani Weeraratna 及同事去考虑衰老微环境在肿瘤发展中所起作用。
癌症的发病率随年龄增长而增加，这使得Ashani Weeraratna 及同事去考虑衰老微环境在肿瘤发展中所起作用。 在这项研究中，他们报告说，衰老的成纤维细胞释放 sFRP2 (secreted Frizzled-related protein 2)，它是Wnt信号作用通道的一个调制因子，该因子驱动一个级联，导致转移增加和定向治疗的效果降低。这些发现表明，研究针对特定年龄的癌症治疗方法是有可能的。
Cancer is a disease of ageing. Clinically, aged cancer patients tend to have a poorer prognosis than young. This may be due to accumulated cellular damage, decreases in adaptive immunity, and chronic inflammation. However, the effects of the aged microenvironment on tumour progression have been largely unexplored. Since dermal fibroblasts can have profound impacts on melanoma progression, we examined whether age-related changes in dermal fibroblasts could drive melanoma metastasis and response to targeted therapy. Here we find that aged fibroblasts secrete a Wnt antagonist, sFRP2, which activates a multi-step signalling cascade in melanoma cells that results in a decrease in β-catenin and microphthalmia-associated transcription factor (MITF), and ultimately the loss of a key redox effector, APE1. Loss of APE1 attenuates the response of melanoma cells to DNA damage induced by reactive oxygen species, rendering the cells more resistant to targeted therapy (vemurafenib). Age-related increases in sFRP2 also augment both angiogenesis and metastasis of melanoma cells. These data provide an integrated view of how fibroblasts in the aged microenvironment contribute to tumour progression, offering new possibilities for the design of therapy for the elderly.
来源： Nature 浏览次数：0