Inserm U1016, Cnrs UMR8104, Cochin Institute, Paris 75014 France; Laboratoire de Biologie Cellulaire Comparative des Apicomplexes, Faculté de Médecine, Université Paris Descartes - Sorbonne Paris Cité, France.
Inserm U1016, Cnrs UMR8104, Cochin Institute, Paris 75014 France; Laboratoire de Stress Oxydant, Prolifération Cellulaire et Inflammation, Faculté de Médecine, Université Paris Descartes - Sorbonne Paris Cité, France.
Free Radic Biol Med. 2019 Apr;134:282-287. doi: 10.1016/j.freeradbiomed.2019.01.010. Epub 2019 Jan 9.
Theileria annulata is a protozoan parasite that infects and transforms bovine macrophages causing a myeloid-leukaemia-like disease called tropical theileriosis. TGF-β2 is highly expressed in many cancer cells and is significantly increased in Theileria-transformed macrophages, as are levels of Reactive Oxygen Species (ROS), notably HO. Here, we describe the interplay between TGF-β2 and ROS in cellular transformation. We show that TGF-β2 drives expression of catalase to reduce the amount of HO produced by T. annulata-transformed bovine macrophages, as well as by human lung (A549) and colon cancer (HT-29) cell lines. Theileria-transformed macrophages attenuated for dissemination express less catalase and produce more HO, but regain both virulent migratory and matrigel traversal phenotypes when stimulated either with TGF-β2, or catalase to reduce HO output. Increased HO output therefore, underpins the aggressive dissemination phenotype of diverse tumour cell types, but in contrast, too much HO can dampen dissemination.
环形泰勒虫是一种原生动物寄生虫，可感染并转化牛的巨噬细胞，导致一种称为热带泰勒虫病的髓样白血病样疾病。TGF-β2 在许多癌细胞中高度表达，在环形泰勒虫转化的巨噬细胞中也显著增加，活性氧（ROS）水平，特别是 HO 也是如此。在这里，我们描述了 TGF-β2 和 ROS 在细胞转化中的相互作用。我们表明，TGF-β2 驱动过氧化氢酶的表达，以减少环形泰勒虫转化的牛巨噬细胞以及人肺（A549）和结肠癌细胞（HT-29）系产生的 HO 量。传播减弱的环形泰勒虫转化的巨噬细胞表达的过氧化氢酶较少，产生的 HO 较多，但当用 TGF-β2 或过氧化氢酶刺激以减少 HO 产量时，它们会恢复具有毒力的迁移和基质胶穿透表型。因此，HO 产量的增加是多种肿瘤细胞类型侵袭性传播表型的基础，但相反，过多的 HO 会抑制传播。
