TGF-b2, catalase activity, H2O2 output and metastatic potential of diverse types of tumour

Abstract

Theileria annulata is a protozoan parasite that infects and transforms bovine macrophages causing a myeloid-leukaemia-like disease called tropical theileriosis. TGF-b2 is highly expressed in many cancer cells and is significantly increased in Theileria-transformed macrophages, as are levels of Reactive Oxygen Species (ROS), notably H2O2. Here, we describe the interplay between TGF-b2 and ROS in cellular transformation. We show that TGF-b2 drives expression of catalase to reduce the amount of H2O2 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 H2O2, but regain both virulent migratory and matrigel traversal phenotypes when stimulated with TGF-b2, or catalase that reduce H2O2 output. Increased H2O2 output therefore, underpins the aggressive dissemination phenotype of diverse tumour cell types, but in contrast, too much H2O2 can dampen dissemination.