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Cell-in-cell phenomenon: leukocyte engulfment by non-tumorigenic cells and cancer cell lines
BMC Molecular and Cell Biology ( IF 2.8 ) Pub Date : 2021-07-31 , DOI: 10.1186/s12860-021-00377-3
Mareike F Bauer 1 , Michael Hader 1 , Markus Hecht 1 , Maike Büttner-Herold 2 , Rainer Fietkau 1 , Luitpold V R Distel 1
Affiliation  

Research on cell-in-cell (CIC) phenomena, including entosis, emperipolesis and cannibalism, and their biological implications has increased in recent years. Homotypic and heterotypic engulfment of various target cells by numerous types of host cells has been studied in vitro and in tissue sections. This work has identified proteins involved in the mechanism and uncovered evidence for CIC as a potential histopathologic predictive and prognostic marker in cancer. Our experimental study focused on non-professional phagocytosis of leukocytes. We studied the engulfment of peripheral blood mononuclear cells isolated from healthy donors by counting CIC structures. Two non-tumorigenic cell lines (BEAS-2B, SBLF-9) and two tumour cell lines (BxPC3, ICNI) served as host cells. Immune cells were live-stained and either directly co-incubated or treated with irradiation or with conventional or microwave hyperthermia. Prior to co-incubation, we determined leukocyte viability for each batch via Annexin V-FITC/propidium iodide staining. All host cells engulfed their targets, with uptake rates ranging from 1.0% ± 0.5% in BxPC3 to 8.1% ± 5.0% in BEAS-2B. Engulfment rates of the cancer cell lines BxPC3 and ICNI (1.6% ± 0.2%) were similar to those of the primary fibroblasts SBLF-9 (1.4% ± 0.2%). We found a significant negative correlation between leukocyte viability and cell-in-cell formation rates. The engulfment rate rose when we increased the dose of radiotherapy and prolonged the impact time. Further, microwave hyperthermia induced higher leukocyte uptake than conventional hyperthermia. Using fluorescent immunocytochemistry to descriptively study the proteins involved, we detected ring-like formations of diverse proteins around the leukocytes, consisting, among others, of α-tubulin, integrin, myosin, F-actin, and vinculin. These results suggest the involvement of actomyosin contraction, cell-cell adhesion, and the α-tubulin cytoskeleton in the engulfment process. Both non-tumorigenic and cancer cells can form heterotypic CIC structures by engulfing leukocytes. Decreased viability and changes caused by microwave and X-ray irradiation trigger non-professional phagocytosis.

中文翻译:

细胞内现象:白细胞被非致瘤细胞和癌细胞系吞噬

近年来,对细胞内 (CIC) 现象的研究,包括胞质分裂、自体分裂和同类相食,及其生物学意义的研究有所增加。已经在体外和组织切片中研究了多种类型的宿主细胞对各种靶细胞的同型和异型吞噬。这项工作已经确定了参与该机制的蛋白质,并发现了 CIC 作为癌症潜在组织病理学预测和预后标志物的证据。我们的实验研究侧重于非专业的白细胞吞噬作用。我们通过计数 CIC 结构研究了从健康供体中分离出的外周血单个核细胞的吞噬。两种非致瘤细胞系(BEAS-2B、SBLF-9)和两种肿瘤细胞系(BxPC3、ICNI)作为宿主细胞。免疫细胞被活染色并直接共同孵育或用辐射或常规或微波热疗处理。在共孵育之前,我们通过膜联蛋白 V-FITC/碘化丙啶染色确定了每批的白细胞活力。所有宿主细胞都吞噬了它们的目标,吸收率从 BxPC3 的 1.0% ± 0.5% 到 BEAS-2B 的 8.1% ± 5.0% 不等。癌细胞系 BxPC3 和 ICNI (1.6% ± 0.2%) 的吞噬率与原代成纤维细胞 SBLF-9 (1.4% ± 0.2%) 的吞噬率相似。我们发现白细胞活力与细胞内细胞形成率之间存在显着的负相关。当我们增加放疗剂量和延长撞击时间时,吞没率上升。此外,微波热疗比常规热疗诱导更高的白细胞摄取。使用荧光免疫细胞化学来描述性研究所涉及的蛋白质,我们检测到白细胞周围各种蛋白质的环状结构,其中包括 α-微管蛋白、整联蛋白、肌球蛋白、F-肌动蛋白和纽蛋白。这些结果表明在吞噬过程中涉及肌动球蛋白收缩、细胞间粘附和 α-微管蛋白细胞骨架。非致瘤细胞和癌细胞都可以通过吞噬白细胞形成异型 CIC 结构。微波和 X 射线照射引起的生存能力下降和变化会触发非专业吞噬作用。这些结果表明在吞噬过程中涉及肌动球蛋白收缩、细胞间粘附和 α-微管蛋白细胞骨架。非致瘤细胞和癌细胞都可以通过吞噬白细胞形成异型 CIC 结构。微波和 X 射线照射引起的生存能力下降和变化会触发非专业吞噬作用。这些结果表明在吞噬过程中涉及肌动球蛋白收缩、细胞间粘附和 α-微管蛋白细胞骨架。非致瘤细胞和癌细胞都可以通过吞噬白细胞形成异型 CIC 结构。微波和 X 射线照射引起的生存能力下降和变化会触发非专业吞噬作用。
更新日期:2021-08-01
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