Donati Kim, Sépult Christelle, Rocks Natacha, Blacher Silvia, Gérard Catherine, Noel Agnès, Cataldo Didier
Laboratory of Tumor and Development Biology, Groupe Interdisciplinaire de Génoprotéomique Appliquée-Cancer (GIGA-Cancer), University of Liège, Liège, Belgium.
Laboratory of Pneumology, Groupe Interdisciplinaire de Génoprotéomique Appliquée-Cancer (GIGA-Cancer), University of Liège, Liège, Belgium.
Cancer Growth Metastasis. 2017 Oct 27;10:1179064417738513. doi: 10.1177/1179064417738513. eCollection 2017.
The premetastatic niche in distant organs prior to metastatic cell arrival emerged as an important step in the metastatic cascade. However, molecular mechanisms underlying this process are still poorly understood. In particular, whether neutrophil recruitment at a premetastatic stage promotes or inhibits metastatic cell seeding has to be clarified. We aimed at unraveling how neutrophil infiltration in lung parenchyma induced by the distant primary tumor influences the establishment of lung metastasis. Elevated neutrophil counts and IL-16 levels were found in premetastatic lungs in a syngenic mouse model using 4T1 tumor cells. 4T1 cell-derived soluble factors stimulated IL-16 secretion by neutrophils. The functional contribution of IL-16 is supported by metastasis burden reduction in lungs observed on instillation of an IL-16 neutralizing antibody. Moreover, IL-16 promotes 4T1 cell adhesiveness, invasiveness, and migration. In conclusion, at a premetastatic stage, neutrophil-derived IL-16 favors tumor cell engraftment in lung parenchyma.
在转移细胞到达之前，远处器官中的前转移微环境已成为转移级联反应中的一个重要步骤。然而，这一过程背后的分子机制仍知之甚少。特别是，前转移阶段中性粒细胞的募集是促进还是抑制转移细胞的播种，这一点必须予以阐明。我们旨在揭示远处原发性肿瘤诱导的肺实质中性粒细胞浸润如何影响肺转移的建立。在使用4T1肿瘤细胞的同基因小鼠模型中，在前转移肺中发现中性粒细胞计数和IL-16水平升高。4T1细胞衍生的可溶性因子刺激中性粒细胞分泌IL-16。在注入IL-16中和抗体后观察到肺转移负担减轻，这支持了IL-16的功能作用。此外，IL-16促进4T1细胞的粘附、侵袭和迁移。总之，在前转移阶段，中性粒细胞衍生的IL-16有利于肿瘤细胞在肺实质中的植入。
