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Updated: Oct 8, 2025

A Preclinical Mouse Model of Osteosarcoma to Define the Extracellular Vesicle-mediated Communication Between Tumor and Mesenchymal Stem Cells
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Osteosarcoma exocytosis of soluble LGALS3BP mediates macrophages toward a tumoricidal phenotype

Jing Li1, Chenguang Zhao2, Yuhuan Li1

  • 1Department of Orthopedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, PR China.

Cancer Letters
|December 24, 2021
PubMed

Insights

Osteosarcoma (OS) growth is inhibited by M1 macrophages secreting HSPA1L, impacting tumor cell apoptosis via IRAK pathways. Targeting tumor-associated macrophages (TAMs) offers a novel therapeutic strategy for osteosarcoma.

Area of Science:

  • Oncology
  • Immunology
  • Cell Biology

Background:

  • Osteosarcoma (OS) is a primary bone cancer with a complex tumor microenvironment.
  • Tumor-associated macrophages (TAMs), particularly M1 macrophages, play a crucial role in cancer progression and immune response.
  • Understanding the interaction between OS cells and M1 macrophages is vital for developing new therapeutic strategies.

Purpose of the Study:

  • To investigate the interactions between osteosarcoma cells and M1 macrophages.
  • To elucidate the mechanisms by which M1 macrophages influence osteosarcoma growth.
  • To explore novel therapeutic targets for osteosarcoma treatment.

Main Methods:

  • Utilized transwell co-culture and indirect conditioned medium systems.
  • Established orthotopic osteosarcoma bearing models in vivo.
  • Analyzed the roles of secreted factors like HSPA1L and LGALS3BP and associated signaling pathways (IRAK1/4, Akt).

Main Results:

  • Co-culture of M1 macrophages with OS cells inhibited tumor growth by inducing apoptosis.
  • M1 macrophage-secreted HSPA1L mediated anti-tumor effects via IRAK1 and IRAK4 pathways.
  • OS cell-secreted LGALS3BP induced M1 macrophage Hspa11 secretion via Akt phosphorylation, while LGALS3BP silencing promoted OS progression.

Conclusions:

  • Osteosarcoma modulates macrophage phenotype, influencing OS cell apoptosis through soluble factors.
  • Modulating tumor-associated macrophages presents a promising therapeutic avenue for osteosarcoma.
  • The identified molecular interactions provide potential targets for novel osteosarcoma therapies.
Keywords:
ApoptosisHsp70Lgals3bpMacrophageOsteosarcoma

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