Anaphylatoxin C5a creates a favorable microenvironment for lung cancer progression.
Anaphylatoxin C5a creates a favorable microenvironment for lung cancer progression.
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DOI：
10.4049/jimmunol.1201654
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发表时间：
2012-11-01
期刊：
影响因子：
--
通讯作者：
Pio R
中科院分区：
文献类型：
--
作者：
Corrales L;Ajona D;Rafail S;Lasarte JJ;Riezu-Boj JI;Lambris JD;Rouzaut A;Pajares MJ;Montuenga LM;Pio R
补体系统导致多种免疫和炎症性疾病，包括癌症。在这项研究中，我们调查了肺癌细胞激活补体的能力，并表征了补体激活对肿瘤进展的影响。我们的研究重点是过敏毒素C5a的产生和作用，C5a是补体激活后产生的一种有效的免疫介质。我们首先测量了肺癌细胞系沉积C5和释放C5a的能力。与正常人血清孵育后，肺癌细胞系的C5沉积高于非恶性支气管上皮细胞。有趣的是，即使在没有血清的情况下，肺肿瘤细胞也会产生补体C5a。我们还发现非小细胞肺癌患者血浆中C5a显著升高，这表明C5a的局部产生伴随着其全身扩散。在Lewis肺癌模型中评估C5a对体内肺癌生长的贡献。在接受C5a受体拮抗剂治疗的小鼠中，3LL细胞的同基因肿瘤生长缓慢。C5a在体外不影响3LL细胞的增殖，但可诱导内皮细胞趋化和血管形成。C5a还促进了肿瘤生长所需的免疫抑制微环境。特别是，阻断C5a受体显著减少髓系来源的抑制细胞和免疫调节剂ARG1、CTLA-4、IL6、IL10、LAG3和PDL1(B7H1)。总之，肺癌细胞具有产生C5a的能力，C5a是一种为肺癌进展创造有利肿瘤微环境的分子。
The complement system contributes to various immune and inflammatory diseases, including cancer. In this study we investigated the capacity of lung cancer cells to activate complement, and characterized the consequences of complement activation on tumor progression. We focused our study on the production and role of the anaphylatoxin C5a, a potent immune mediator generated after complement activation. We first measured the capacity of lung cancer cell lines to deposit C5 and release C5a. C5 deposition, after incubation with normal human serum, was higher in lung cancer cell lines than in non-malignant bronchial epithelial cells. Interestingly, lung malignant cells produced complement C5a even in the absence of serum. We also found a significant increase of C5a in plasma from patients with non-small cell lung cancer, suggesting that the local production of C5a is followed by its systemic diffusion. The contribution of C5a to lung cancer growth in vivo was evaluated in the Lewis lung cancer model. Syngeneic tumors of 3LL cells grew slower in mice treated with an antagonist of the C5a receptor. C5a did not modify 3LL cell proliferation in vitro but induced endothelial cell chemotaxis and blood-vessels formation. C5a also contributed to the immunosuppressive microenvironment required for tumor growth. In particular, blockade of C5a receptor significantly reduced myeloid-derived suppressor cells and immunomodulators ARG1, CTLA-4, IL6, IL10, LAG3 and PDL1 (B7H1). In conclusion, lung cancer cells have the capacity to generate C5a, a molecule that creates a favorable tumor microenvironment for lung cancer progression.
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DOI：
10.1073/pnas.171320598
发表时间：
2001-08-14
影响因子：
11.1
作者：
Brichory, FM;Misek, DE;Hanash, SM
通讯作者：
Hanash, SM
影响因子：
4.4
作者：
Ajona, Daniel;Hsu, Yi-Fan;Pio, Ruben
通讯作者：
Pio, Ruben
影响因子：
11.5
作者：
Konishi, J;Yamazaki, K;Nishimura, M
通讯作者：
Nishimura, M
影响因子：
20.3
作者：
Langer, Harald F.;Chung, Kyoung-Jin;Chavakis, Triantafyllos
通讯作者：
Chavakis, Triantafyllos
DOI：
10.1016/s0162-3109(99)00178-2
发表时间：
2000-03-01
期刊：
IMMUNOPHARMACOLOGY
影响因子：
--
作者：
Jagels, MA;Daffern, PJ;Hugli, TE
通讯作者：
Hugli, TE