INTERCELLULAR INDUCTION OF APOPTOSIS SIGNALLING PATHWAYS

Intercellular signalling plays an important role in the progression of a transformed cell to a tumour. In order to characterise the underlying mechanisms, a well-defined model cell system of intercellular induction of apoptosis was used where neighbouring normal cells can selectively eliminate transformed cells. In the absence of non-transformed cells, the induction of apoptosis in transformed 208Fsrc3 cells occurs via autocrine destruction and is dominated by peroxidase (PO), which initiates the PO/hypochlorous acid signalling pathway at high local cell densities. However, when the transformed cells are co-cultured with the non-transformed 208F cells, apoptosis in transformed cells additionally occurs as a result of intercellular signalling with the non-transformed cells and is predominantly due to the production of nitric oxide (NO center dot), which initiates the NO center dot/peroxynitrite pathway.