VHL and clear cell renal carcinoma: Importantly, deletion of the VHL gene specifically in kidney tubule cells in mice (approximately 70% of clear cell renal carcinoma have inactivating mutation of VHL) induces production of OSM which in turn pushes kidney endothelial cells into an endothelial-to-mesenchymal transition to support VHL-defective tubule cell transformation and promote macrophage polarization towards a tissue-supportive M2-like phenotype (49).