Gastric Cancer:源自肥大细胞的白介素-17A通过腹膜扩散促进胃癌的纤维化

2020-08-07 MedSci原创 MedSci原创

胃癌是全世界癌症死亡的最常见疾病之一, 在胃癌中最常见的转移是腹膜扩散,会导致预后不佳。

        胃癌是全世界癌症死亡的最常见疾病之一, 在胃癌中最常见的转移是腹膜扩散,会导致预后不佳,腹膜扩散的特征是癌细胞扩散并在腹膜空间内基质纤维化,而腹膜扩散造成的纤维组织会引起致命的疾病,如肠梗阻,黄疸和肾积水,导致吸入性肺炎,肝功能衰竭和肾功能衰竭,这是死亡的直接原因。因此,控制腹膜弥漫性纤维化对于改善治疗效果是必要的。

        白介素-17A(IL-17A)在各种肿瘤组织中普遍存在,是一种抑制肿瘤的免疫监视生物标志物,尽管长期以来一直认为IL-17A的主要细胞来源是CD4阳性T淋巴细胞(Th17细胞),但最近有几项研究报道了多种适应性和先天性免疫细胞类型,包括γδT细胞,自然杀伤(NK)T细胞,NK细胞,肥大细胞和粒细胞也产生IL-17A。胃癌原发灶中IL-17A的主要来源是肥大细胞,肥大细胞分泌的IL-17A的数量与总体存活率低相关。因此,在本项研究中我们探究了哪些细胞是IL-17A的主要来源,以及在胃癌的腹膜扩散中组织纤维化与IL-17A之间的关系。

        研究人员对70例腹膜扩散性胃癌患者进行了相关试验。通过免疫荧光和免疫组织化学检查IL-17A与纤维化之间的相关性。同时基于共培养细胞(HPMC和人胃癌细胞系MKN-45)将肿瘤细胞皮下移植到裸鼠背侧,建立了纤维化肿瘤模型。探究用或不用IL-17A治疗小鼠的效果。

        研究结果显示肥大显著想表达IL-17A,肥大细胞类胰蛋白酶(MCT)阳性细胞数量与纤维化程度之间存在显着相关性(r  = 0.417,P  <0.01)。在小鼠模型中,IL-17A增强了肿瘤的进展和纤维化。此外,用IL-17A处理的人腹膜间皮细胞显示出增加的迁移现象。

        因此,我们可以判断来源于肥大细胞的IL-17A在胃癌的腹膜扩散中促进肿瘤纤维化,抑制肥大细胞脱粒可能是控制器官纤维化的有前途的治疗策略。

 

原始出处:

Katsuya Gunjigake. Et al. Interleukin-17A derived from mast cells contributes to fibrosis in gastric cancer with peritoneal dissemination. Gastric Cancer.2020.

 

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    2020-12-25 skhzy
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    2021-05-16 许安
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createdBy=a8312408082, createdName=chenny, createdTime=Fri Aug 07 10:38:58 CST 2020, time=2020-08-07, status=1, ipAttribution=)]
    2020-08-09 xuyong530
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createdBy=a8312408082, createdName=chenny, createdTime=Fri Aug 07 10:38:58 CST 2020, time=2020-08-07, status=1, ipAttribution=)]
    2020-08-07 chenny

    学习了

    0

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