Culture supernatants of cervical cancer cells induce an M2 phenotypic profile in THP-1 macrophages

Culture supernatants of cervical cancer cells induce an M2 phenotypic profile in THP-1 macrophages
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DOI:
10.1016/j.cellimm.2016.07.001
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发表时间:
2016-12-01
影响因子:
4.3
通讯作者:
Cesar Ortiz-Lazareno, Pablo
Cesar Ortiz-Lazareno, Pablo
中科院分区:
医学4区
文献类型:
--
作者:
Julia Pedraza-Brindis, Eliza;Sanchez-Reyes, Karina;Cesar Ortiz-Lazareno, Pablo

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宫颈癌(CxCa)患者通常呈现肿瘤相关巨噬细胞浸润,这与不良预后相关。我们发现宫颈癌细胞系(HeLa、SiHa和C - 33A)分泌参与调节肿瘤生长的因子,包括白细胞介素 - 6、白细胞介素 - 4、血小板源性生长因子(AA)、肝细胞生长因子、血管内皮生长因子、血管生成素 - 2和转化生长因子 - β3。我们评估了这些细胞系的培养上清液对源自THP - 1细胞系的巨噬细胞的影响。用宫颈癌细胞培养上清液处理的巨噬细胞呈现出M2样表型,表现为CD163表达、一氧化氮释放量低以及白细胞介素 - 6、血小板源性生长因子(AA)、肝细胞生长因子、血管生成素 - 2和血管内皮生长因子的高分泌。在去除宫颈癌细胞培养上清液48小时后,巨噬细胞继续产生血小板源性生长因子(AA)、血小板源性生长因子(BB)和血管内皮生长因子。体内M2巨噬细胞的诱导有利于肿瘤生长、血管生成、组织重塑和转移。这些结果表明,宫颈癌细胞分泌的因子在THP - 1巨噬细胞中诱导出稳定的M2表型。(C)2016爱思唯尔公司。保留所有权利。
Patients with cervical cancer (CxCa) typically present an infiltrate of tumor-associated macrophages, which is associated with a poor prognosis. We found that CxCa cell lines (HeLa, SiHa, and C-33A) secreted factors involved in regulating tumor growth including IL-6, IL-4, PDGF(AA), HGF, VEGF, ANG-2, and TGF-beta 3. We assessed the effects of culture supernatants from these cell lines on macrophages derived from the THP-1 cell line. Macrophages treated with culture supernatants from CxCa cells developed an M2-like phenotype with expression of CD163, low nitric oxide release, and high secretion of IL-6, PDGF(AA), HGF, ANG-2, and VEGF. The macrophages continued to produce PDGF(AA), PDGF(BB), and VEGF 48 h after the CxCa cell culture supernatants were removed. The induction of M2 macrophages in vivo favors tumor growth, angiogenesis, tissue remodeling, and metastasis. These results demonstrated that factors secreted by CxCa cells induced a stable M2 phenotype in THP-1 macrophages. (C) 2016 Elsevier Inc. All rights reserved.