Gene expression profile of F4/80+ cells isolated from tumors implanted in wild type and St2-/- mouse. Mus musculus

We report a novel mechanism of the interaction between perivascular cell and TAMs in promoting metastasis through the IL-33-ST2-dependent pathway. IL-33 was the highest up-regulated gene through activation of SOX7 transcription factor in PDGF-BB-stimulated pericytes. Gain- and loss-of-function experiments validate that IL-33 promotes metastasis through recruitment of TAMs. Il33-/- deficient mice showed impaired TAM recruitment and metastasis. Pharmacological inhibition of the IL-33-ST2 signalling by a soluble ST2 significantly inhibited TAMs and metastasis. Genetic deletion of host IL-33 in mice also blocked PDGF-BB-induced TAM recruitment and metastasis. High IL-33 in human cancers correlated with poor survival prognosis. These findings shed novel mechanisms of tumour stroma in promoting metastasis and have therapeutic implications for cancer therapy. Overall design: F4/80+ cells are isolated from tumors implanted in wild type and St2-/- mouse (n=3 samples/group)