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A Preclinical Mouse Model of Osteosarcoma to Define the Extracellular Vesicle-mediated Communication Between Tumor and Mesenchymal Stem Cells
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Dendritic Cells Drive Osteosarcomagenesis through Newly Identified Oncogene and Tumor Suppressor

Kevin B Jones1

  • 1Departments of Orthopaedics and Oncological Sciences, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah. Kevin.jones@hci.utah.edu.

Cancer Discovery
|November 3, 2019
PubMed

Insights

The study investigated GRM4 and IL23 in osteosarcoma, finding they influence tumor-infiltrating myeloid cells, not cancer cells. This suggests a new therapeutic target for osteosarcoma treatment.

Area of Science:

  • Oncology
  • Immunology
  • Genetics

Background:

  • The gene GRM4 is suspected to be a tumor suppressor based on Genome-Wide Association Studies (GWAS).
  • Interleukin-23 (IL23) is a cytokine implicated in various cancers and is investigated as a potential oncogene.
  • Osteosarcoma is a primary bone cancer with complex genetic and cellular interactions.

Purpose of the Study:

  • To investigate the roles of GRM4 and IL23 in a mouse model of osteosarcomagenesis.
  • To determine the cellular context in which GRM4 and IL23 exert their functions within the tumor microenvironment.
  • To explore the potential of targeting these genes or their associated pathways in osteosarcoma.

Main Methods:

  • Utilized a mouse model to study osteosarcomagenesis.
  • Analyzed the expression patterns of GRM4 and IL23 within the tumor microenvironment.
  • Investigated the cellular localization and functional impact of GRM4 and IL23 on different cell types within the tumor.

Main Results:

  • Both GRM4 and IL23 were found to be expressed in tumor-infiltrating myeloid-derived antigen-presenting cells.
  • The primary influence of GRM4 and IL23 was observed within these myeloid cells, rather than directly within osteosarcoma cells.
  • This indicates a significant role for the tumor microenvironment, specifically myeloid-derived cells, in osteosarcoma development and progression.

Conclusions:

  • GRM4 and IL23 play crucial roles in the tumor microenvironment, particularly within myeloid-derived antigen-presenting cells.
  • Their influence on osteosarcomagenesis occurs through these immune cells, suggesting a non-cell-autonomous mechanism.
  • Targeting GRM4 or IL23 within the tumor-infiltrating myeloid compartment may represent a novel therapeutic strategy for osteosarcoma.

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