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Updated: Jan 10, 2026

Three-Dimensional Bone Extracellular Matrix Model for Osteosarcoma
08:07

Three-Dimensional Bone Extracellular Matrix Model for Osteosarcoma

Published on: April 12, 2019

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Transcriptomic analysis reveals TME-mediated macrophage IFIT1 upregulation and CX3CR1 suppression drive osteosarcoma

Keyi Wang1, Huanyang He1, Jiamin Liang1

  • 1Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed by the Province and Ministry, Department of Orthopedics Trauma and Hand Surgery, Guangxi Key Laboratory of Regenerative Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.

Frontiers in Oncology
|November 21, 2025
PubMed
Abstract

Insights

Osteosarcoma tumor microenvironment alters macrophage gene expression. Upregulating IFIT1 and downregulating CX3CR1 accelerates osteosarcoma progression, offering new therapeutic targets.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Osteosarcoma (OS) is a prevalent bone tumor with poor patient prognosis.
  • Conventional treatments for OS have stagnated, prompting research into novel therapeutic targets.
  • The tumor microenvironment (TME) and tumor-associated macrophages (TAM) are emerging as key areas of investigation.

Purpose of the Study:

  • To investigate how the OS TME influences macrophage gene expression.
  • To identify potential therapeutic targets within the OS TME for improved treatment strategies.

Main Methods:

  • Bone marrow-derived macrophages (BMMs) were cultured with K7M2 conditional medium (CM) to analyze gene expression changes via RNA sequencing.
  • Single-cell sequencing and PCR were employed to assess IFIT1 and CX3CR1 expression levels.
  • Functional validation was conducted using flow cytometry, cloning, wound healing, and transwell assays with specific inhibitors.

Main Results:

  • Exposure to OS TME altered BMM morphology and transcriptome, revealing complex interactions among differentially expressed genes.
  • A representative finding was the upregulation of IFIT1 and downregulation of CX3CR1.
  • Inhibiting CX3CR1 promoted TAM polarization and accelerated osteosarcoma progression; increasing IFIT1 also enhanced osteosarcoma growth.

Conclusions:

  • The OS TME significantly modifies macrophage gene expression.
  • These findings provide a cellular and molecular basis for exploring novel therapeutic targets in osteosarcoma treatment.
Keywords:
CX3CR1IFIT1osteosarcoma microenvironmenttranscriptome analysistumor-associated macrophages

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