TGF-β2, catalase activity, HO output and metastatic potential of diverse types of tumour.

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.