Infiltrating Macrophages Induced Stem-cell-like Features Through PI3K/AKT/GSK3β Signaling to Promote Neurofibroma Growth

Jing Jia; Haibao Zhang; Hongke Zhang; Wenbo Liu; Maoguo Shu

doi:10.1016/j.arcmed.2019.12.018

Infiltrating Macrophages Induced Stem-cell-like Features Through PI3K/AKT/GSK3β Signaling to Promote Neurofibroma Growth

Arch Med Res. 2020 Feb;51(2):124-134. doi: 10.1016/j.arcmed.2019.12.018. Epub 2020 Feb 25.

Authors

Jing Jia¹, Haibao Zhang², Hongke Zhang³, Wenbo Liu³, Maoguo Shu⁴

Affiliations

¹ Department of Plastic, Cosmetic and Maxillofacial Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China; The school of electronic and information engineering, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
² Key laboratory for Tumor Precision Medicine of Shaanxi Province, Xi'an, Shaanxi, China.
³ Department of Plastic, Cosmetic and Maxillofacial Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
⁴ Department of Plastic, Cosmetic and Maxillofacial Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China. Electronic address: maoguo_shu@126.com.

PMID: 32111496
DOI: 10.1016/j.arcmed.2019.12.018

Abstract

Background: Inflammation plays an important role in promoting neurofibroma progression, and macrophages are key inflammatory cells in neurofibroma.

Aim of this study: We attempted to clarify the detailed mechanism of infiltrating macrophages promoting neurofibroma progression.

Methods: We performed IHC and Western blot assays to detect the expression levels of OCT3/4, Nanog and SOX2 in tissues and cells. A colony/sphere formation assay was used to analyze cell stemness. MTT, colony formation assay and xenograft tumor model were used to detect cell growth. The transwell system was used to examine macrophage infiltration.

Results: We demonstrated increased macrophage infiltration in neurofibroma tissues accompanied by increased stem cell-like markers. Moreover, Nf1-mutated SW10 cells possessed a stronger capacity to recruit macrophages, which in turn facilitated neurofibroma growth. Mechanistically, the infiltrating macrophages induced neurofibroma cell stem cell transition by modulating PI3K/AKT/GSK3β signaling, which then enhanced neurofibroma cell viability in vivo and in vitro.

Conclusion: Our results revealed a new mechanism of infiltrating macrophages contributing to neurofibroma progression, and targeting this newly identified signaling may help to treat neurofibroma.

Keywords: Macrophage; Neurofibroma; PI3K/AKT/GSK3β signaling; Stem cell transition.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Proliferation
Glycogen Synthase Kinase 3 beta / metabolism*
Humans
Macrophages / metabolism
Mice
Neurofibroma / genetics*
Phosphatidylinositol 3-Kinases / metabolism*
Proto-Oncogene Proteins c-akt / metabolism*
Signal Transduction

Substances

Glycogen Synthase Kinase 3 beta
Proto-Oncogene Proteins c-akt