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Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
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MMP-9 secreted by M2-type macrophages promotes Wilms' tumour metastasis through the PI3K/AKT pathway

Kaixuan Tian1,2, Guoqiang Du2, Xiaoqing Wang2

  • 1Department of Pediatric Orthopaedics, The Third Hospital of Hebei Medical University, Shijiazhuang, 050051, Hebei, People's Republic of China.

Molecular Biology Reports
|February 2, 2022
PubMed
Abstract

Insights

M2 macrophages promote Wilms' tumour growth and spread by releasing MMP9, which drives epithelial-mesenchymal transition via the PI3K/AKT pathway. High MMP9 levels in tumour tissue indicate a poor prognosis for childhood cancer patients.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Wilms' tumour (WT) is a common childhood kidney cancer.
  • Tumour-associated macrophages (TAMs) are linked to poor prognosis in WT, but their exact role is unclear.
  • Understanding TAMs' protumorigenic mechanisms is crucial for improving WT treatment.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which TAMs promote Wilms' tumour progression.
  • To investigate the role of Matrix metalloproteinase 9 (MMP9) in TAM-mediated WT growth and metastasis.

Main Methods:

  • Polarization of TAMs into M1 and M2 subtypes and co-culture with WT cells.
  • Assessment of cell viability, invasion, and MMP9 expression.
  • Analysis of MMP9 distribution in WT tissues and correlation with patient survival data.

Main Results:

  • M2 macrophages significantly enhanced WT cell viability and invasion compared to M1 macrophages.
  • M2 macrophages exhibited higher MMP9 expression, which was elevated in WT tissues.
  • MMP9 activated the PI3K/AKT pathway, promoting epithelial-mesenchymal transition (EMT), proliferation, and invasion in WT.
  • High MMP9 expression correlated with poor patient survival.

Conclusions:

  • M2-type TAMs promote Wilms' tumour proliferation and metastasis.
  • This occurs via MMP9 secretion, which enhances EMT through the PI3K/AKT pathway.
  • MMP9 serves as a potential biomarker for poor prognosis in Wilms' tumour.
Keywords:
Epithelial-mesenchymal transitionMMP-9Tumour-associated macrophagesWilms’ tumour

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