Paracrine signals of the tumour niche control the growth of tumours, either directly or by modulation of an anti-tumour immune response. Several of these paracrine factors are produced as membrane-bound proteins and need to be released by limited proteolysis.
Members of the a disintegrin and metalloprotease (ADAM) family of transmembrane proteases are major mediators of cytokine and growth factor release. I will discuss the potential role of ADAM proteases in shaping a tumour permissive niche. I will provide evidence that within the tumour micro-environment the family member ADAM17 is a major promoter of primary tumour growth and metastasis through initiation of TNF-mediated necroptosis, the release of EGF receptor ligands and the induction of IL-6/GP130 trans-signalling. In this context I will discuss the controversial role of IL-6 family cytokines in the control of tumour growth. By using a novel mouse model of cell-autonomous IL-6/GP130 signalling, I will provide evidence that this might be linked to cell type-specific signalling of these cytokines. Based on our findings I will discuss potential novel therapeutic strategies.