C3 Drives Inflammatory Skin Carcinogenesis Independently of C5.
C3 Drives Inflammatory Skin Carcinogenesis Independently of C5.
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C3独立于C5驱动炎性皮肤癌变。
DOI：
10.1016/j.jid.2020.06.025
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Botto M
中科院分区：
文献类型：
--
作者：
Jackson WD;Gulino A;Fossati-Jimack L;Castro Seoane R;Tian K;Best K;Köhl J;Belmonte B;Strid J;Botto M
非黑色素瘤皮肤癌，如皮肤鳞状细胞癌（cSCC）是最常见的癌症形式，可能是紫外线或化学致癌物对上皮细胞的DNA损伤的结果。越来越多的证据表明，补体系统参与癌症免疫监视;然而，其在cSCC中的作用仍不清楚。在这里，我们发现补体基因在cSCC患者的组织中表达，C3激活片段存在于cSCC活检组织中，表明补体激活。在化学诱导的cSCC的两阶段小鼠模型中使用一系列补体缺陷小鼠，其中亚临床剂量的7，12-二甲基苯并[a]蒽导致上皮细胞中的致癌突变，并且12-O-十四烷酰基佛波醇-13-乙酸酯促进这些细胞的生长，我们发现C3缺陷小鼠显示出显著降低的肿瘤负荷，而在缺乏C5 aR 1的小鼠中观察到相反的表型，C5 aR 2和C3 a受体。此外，在不能形成膜攻击复合物的小鼠中，肿瘤进展没有改变。C3缺乏并不影响癌症对7，12-二甲基苯并[a]蒽单独治疗的反应，但在12-O-十四烷酰佛波醇-13-乙酸酯诱导的炎症过程中减少了表皮增生。总的来说，这些数据表明C3在慢性皮肤炎症期间驱动肿瘤发生，独立于C5 a或膜攻击复合物的下游产生。
Nonmelanoma skin cancer such as cutaneous squamous cell carcinoma (cSCC) is the most common form of cancer and can occur as a consequence of DNA damage to the epithelium by UVR or chemical carcinogens. There is growing evidence that the complement system is involved in cancer immune surveillance; however, its role in cSCC remains unclear. Here, we show that complement genes are expressed in tissue from patients with cSCC, and C3 activation fragments are present in cSCC biopsies, indicating complement activation. Using a range of complement-deficient mice in a two-stage mouse model of chemically-induced cSCC, where a subclinical dose of 7,12-dimethylbenz[a]anthracene causes oncogenic mutations in epithelial cells and 12-O-tetradecanoylphorbol-13-acetate promotes the outgrowth of these cells, we found that C3-deficient mice displayed a significantly reduced tumor burden, whereas an opposite phenotype was observed in mice lacking C5aR1, C5aR2, and C3a receptor. In addition, in mice unable to form the membrane attack complex, the tumor progression was unaltered. C3 deficiency did not affect the cancer response to 7,12-dimethylbenz[a]anthracene treatment alone but reduced the epidermal hyperplasia during 12-O-tetradecanoylphorbol-13-acetate–induced inflammation. Collectively, these data indicate that C3 drives tumorigenesis during chronic skin inflammation, independently of the downstream generation of C5a or membrane attack complex.
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影响因子：
30.5
作者：
Crawford G;Hayes MD;Seoane RC;Ward S;Dalessandri T;Lai C;Healy E;Kipling D;Proby C;Moyes C;Green K;Best K;Haniffa M;Botto M;Dunn-Walters D;Strid J
通讯作者：
Strid J
影响因子：
5.4
作者：
ARBEIT, JM;MUNGER, K;HANAHAN, D
通讯作者：
HANAHAN, D
影响因子：
15.9
作者：
HALPERIN, JA;TARATUSKA, A;NICHOLSONWELLER, A
通讯作者：
NICHOLSONWELLER, A
DOI：
10.4049/jimmunol.1201654
发表时间：
2012-11-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Corrales L;Ajona D;Rafail S;Lasarte JJ;Riezu-Boj JI;Lambris JD;Rouzaut A;Pajares MJ;Montuenga LM;Pio R
通讯作者：
Pio R
影响因子：
64.8
作者：
Chen, Nien-Jung;Mirtsos, Christine;Yeh, Wen-Chen
通讯作者：
Yeh, Wen-Chen