中性粒细胞胞外陷阱在结肠癌中的梯度浸润及其参与肿瘤生长的证据
Gradient Infiltration of Neutrophil Extracellular Traps in Colon Cancer and Evidence for Their Involvement in Tumour Growth.
作者信息
Arelaki Stella, Arampatzioglou Athanasios, Kambas Konstantinos, Papagoras Charalampos, Miltiades Paraskevi, Angelidou Iliana, Mitsios Alexandros, Kotsianidis Ioannis, Skendros Panagiotis, Sivridis Efthimios, Maroulakou Ioanna, Giatromanolaki Alexandra, Ritis Konstantinos
机构信息
Department of Pathology, University General Hospital of Alexandroupolis, Alexandroupolis, Greece.
Laboratory of Molecular Hematology, Democritus University of Thrace, Alexandroupolis, Greece.
出版信息
PLoS One. 2016 May 2;11(5):e0154484. doi: 10.1371/journal.pone.0154484. eCollection 2016.
BACKGROUND
The role of neutrophils in tumour biology is largely unresolved. Recently, independent studies indicated either neutrophil extracellular traps (NETs) or Tissue Factor (TF) involvement in cancer biology and associated thrombosis. However, their individual or combined role in colonic adenocarcinoma is still unexplored.
METHODS
Colectomy tissue specimens and variable number of draining lymph nodes were obtained from ten patients with adenocarcinoma of the colon. NETs deposition and neutrophil presence as well as TF expression were examined by immunostaining. The effect of NETs on cancer cell growth was studied in in vitro co-cultures of Caco-2 cell line and acute myeloid leukemia primary cells. Proliferation and apoptosis/necrosis of cancer cells were analyzed by flow cytometry.
RESULTS
TF-bearing NETs and neutrophil localization were prominent in tumour sections and the respective metastatic lymph nodes. Interestingly, neutrophil infiltration and NETs concentration were gradually reduced from the tumour mass to the distal margin. The in vitro-generated NETs impeded growth of cancer cell cultures by inducing apoptosis and/or inhibiting proliferation.
CONCLUSIONS
These data support further the role of neutrophils and NETs in cancer biology. We also suggest their involvement on cancer cell growth.
背景
中性粒细胞在肿瘤生物学中的作用在很大程度上尚未明确。最近，独立研究表明中性粒细胞胞外诱捕网（NETs）或组织因子（TF）参与癌症生物学及相关血栓形成。然而，它们在结肠腺癌中的单独或联合作用仍未得到探索。
方法
从10例结肠腺癌患者处获取结肠切除组织标本及不同数量的引流淋巴结。通过免疫染色检测NETs沉积、中性粒细胞存在情况以及TF表达。在Caco-2细胞系与急性髓系白血病原代细胞的体外共培养中研究NETs对癌细胞生长的影响。通过流式细胞术分析癌细胞的增殖及凋亡/坏死情况。
结果
携带TF的NETs及中性粒细胞定位在肿瘤切片及相应转移淋巴结中很突出。有趣的是，从肿瘤块到远端边缘，中性粒细胞浸润及NETs浓度逐渐降低。体外生成的NETs通过诱导凋亡和/或抑制增殖阻碍癌细胞培养的生长。
结论
这些数据进一步支持了中性粒细胞和NETs在癌症生物学中的作用。我们还提示它们参与癌细胞生长。
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