Sexual dimorphism of liver metastasis by murine pancreatic neuroendocrine tumors is affected by expression of complement C5.
Sexual dimorphism of liver metastasis by murine pancreatic neuroendocrine tumors is affected by expression of complement C5.
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DOI：
10.18632/oncotarget.8874
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发表时间：
2016-05-24
期刊：
影响因子：
--
通讯作者：
Harris CR
中科院分区：
文献类型：
--
作者：
Contractor T;Kobayashi S;da Silva E;Clausen R;Chan C;Vosburgh E;Tang LH;Levine AJ;Harris CR
在胰腺神经内分泌肿瘤(PanNETs)的小鼠模型中，男性发生肝转移的频率更高。雄性小鼠的血清和瘤内天然免疫蛋白补体C5水平也较高。在丧失表达补体C5能力的小鼠中，转移的频率较低，并且雄性不再比雌性更高的转移频率。补体C5a受体C5aR1/CD88的小分子拮抗剂PMX53治疗也减少了转移。缺乏补体C5功能基因的小鼠原发肿瘤较小，侵袭性较小，并且缺乏CD68+巨噬细胞，而CD68+巨噬细胞以前与此类肿瘤的转移有关。这是第一次在小鼠模型中报道导致转移的性别二型性的基因。在人类疾病中，临床晚期肿瘤比低级肿瘤表达更多的补体C5，这种疾病也表现出性别二型性转移。
In a mouse model for neuroendocrine tumors of the pancreas (PanNETs), liver metastasis occurred at a higher frequency in males. Male mice also had higher serum and intratumoral levels of the innate immunity protein complement C5. In mice that lost the ability to express complement C5, there was a lower frequency of metastasis, and males no longer had a higher frequency of metastasis than females. Treatment with PMX53, a small molecule antagonist of C5aR1/CD88, the receptor for complement C5a, also reduced metastasis. Mice lacking a functional gene for complement C5 had smaller primary tumors, which were less invasive and lacked the CD68+ macrophages that have previously been associated with metastasis in this type of tumor. This is the first report of a gene that causes sexual dimorphism of metastasis in a mouse model. In the human disease, which also shows sexual dimorphism for metastasis, clinically advanced tumors expressed more complement C5 than less advanced tumors.
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DOI：
10.1084/jem.160.2.411
发表时间：
1984-08-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Baba A;Fujita T;Tamura N
通讯作者：
Tamura N
影响因子：
64.5
作者：
Li Z;Tuteja G;Schug J;Kaestner KH
通讯作者：
Kaestner KH
影响因子：
50.3
作者：
Casanovas, O;Hicklin, DJ;Hanahan, D
通讯作者：
Hanahan, D
影响因子：
6.5
作者：
Joosse, Arjen;de Vries, Esther;Engel, Jutta
通讯作者：
Engel, Jutta
影响因子：
64.8
作者：
HANAHAN, D
通讯作者：
HANAHAN, D