Wislez Marie, Antoine Martine, Rabbe Nathalie, Gounant Valérie, Poulot Virginie, Lavolé Armelle, Fleury-Feith Jocelyne, Cadranel Jacques
Services de Pneumologie, AP-HP, Hôpital Tenon, Paris, France.
Clin Cancer Res. 2007 Jun 15;13(12):3518-27. doi: 10.1158/1078-0432.CCR-06-2558.
Adenocarcinoma with bronchioloalveolar carcinoma (BAC) features is a subtype of non-small cell lung cancers characterized by an intense inflammatory reaction composed of macrophages and neutrophils and by a distinct natural history with intrapulmonary spread leading to death due to respiratory failure. We hypothesized that neutrophils could promote aerogenous spread of lung adenocarcinoma with BAC features.
We examined the effect of neutrophils on A549 cell line detachment in vitro and we quantified desquamation of tumor cells on tumor tissue (n = 25) and on matched bronchioloalveolar lavage (n = 17) in vivo in a series of patients with adenocarcinoma with BAC features.
Neutrophils induced A549 detachment mediated by signals through cell-to-cell contact. Detached A549 cells were still viable and able to proliferate in vitro. Neutralization studies identified several membrane-bound molecules involved in detachment (i.e., intercellular adhesion molecule-1/lymphocyte function-associated antigen-1, tumor necrosis factor alpha/tumor necrosis factor alpha receptor inhibitor, interleukin-1alpha /interleukin-1alpha receptor, and neutrophil elastase). In tumor tissue, shedding was detected in all samples, with a median shedding score of 42% (range, 4-95%). Micropapillary clusters were detected in 23 of the 25 tumor tissue samples, with a median micropapillary score of 1.40 (range, 0-2.1), and tumor cells were detected in 7 of 17 lavages. The micropapillary score was associated with a high neutrophil count in bronchioloalveolar lavage (P = 0.051). The shedding cell percentage was a significant factor in shorter survival (P = 0.034, univariate Cox analysis).
Tumor shedding is induced by neutrophils. It is a significant factor of shorter survival and may be an important event in adenocarcinoma progression.
具有细支气管肺泡癌（BAC）特征的腺癌是非小细胞肺癌的一种亚型，其特征为巨噬细胞和中性粒细胞组成的强烈炎症反应以及独特的自然病程，即肺内播散导致呼吸衰竭死亡。我们推测中性粒细胞可促进具有BAC特征的肺腺癌的气源性播散。
我们在体外检测了中性粒细胞对A549细胞系脱离的影响，并在一系列具有BAC特征的腺癌患者体内，对肿瘤组织（n = 25）和配对的支气管肺泡灌洗样本（n = 17）中的肿瘤细胞脱落情况进行了定量分析。
中性粒细胞通过细胞间接触信号介导诱导A549细胞脱离。脱离的A549细胞仍具有活力且能够在体外增殖。中和研究确定了几种参与细胞脱离的膜结合分子（即细胞间黏附分子-1/淋巴细胞功能相关抗原-1、肿瘤坏死因子α/肿瘤坏死因子α受体抑制剂、白细胞介素-1α/白细胞介素-1α受体和中性粒细胞弹性蛋白酶）。在肿瘤组织中，所有样本均检测到细胞脱落，脱落评分中位数为42%（范围为4%-95%）。25个肿瘤组织样本中有23个检测到微乳头簇，微乳头评分中位数为1.40（范围为0-2.1），17例灌洗样本中有7例检测到肿瘤细胞。微乳头评分与支气管肺泡灌洗中高中性粒细胞计数相关（P = 0.051）。脱落细胞百分比是生存时间较短的一个重要因素（P = 0.034，单因素Cox分析）。
中性粒细胞诱导肿瘤细胞脱落。它是生存时间较短的一个重要因素，可能是腺癌进展中的一个重要事件。
