MMP-9 secreted by M2-type macrophages promotes Wilms' tumour metastasis through the PI3K/AKT pathway.

Abstract

Wilms' tumour (WT) is a malignant tumour of childhood with the typical symptoms of an abdominal mass. Tumour-associated macrophages (TAMs) accumulate and imply a poor prognosis in WT, but the mechanism of how TAMs affect the prognosis has not been fully elucidated. In this study, we aimed to present the molecular mechanisms underlying the protumorigenic capacities of TAMs in WT. TAMs were polarized into M1- and M2-type macrophages. The two types of macrophages were cocultured with SK-NEP-1 cells, and their cell viability and invasion ability were measured. Matrix metalloproteinase 9 (MMP9) expression was assessed in different types of macrophages, and the role of MMP9 in WT was explored. Then data from children diagnosed with WT in our department between February 2006 and July 2014 were retrospectively analysed, the tumour tissues were analysed to explore the distribution of MMP9. Kaplan-Meier analysis of the relationship between MMP9 expression and follow-up information was performed. The results showed that M2-type macrophages could improve the viability and invasive ability of SK-NEP-1 cells. MMP9 expression in M2-type macrophages was significantly higher than that in M1-type macrophages. MMP9 could activate the AKT/PI3K signalling pathway to initiate the epithelial-mesenchymal transition (EMT) process, and promote the proliferation and invasion of WT. In WT tissue, the MMP9 expression level was elevated and it was located in the tumour stroma, which was the same as M2-type macrophage location, and a high level of MMP9 predicted poor survival. M2-type macrophages facilitate tumour proliferation and metastasis by secreting MMP9 to enhance the EMT process via a PI3K/AKT dependent pathway in Wilms' tumour.