Related Experiment Video

Updated: Aug 6, 2025

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

Three-Dimensional Bone Extracellular Matrix Model for Osteosarcoma

Published on: April 12, 2019

7.3K

Osteosarcoma-enriched transcripts paradoxically generate osteosarcoma-suppressing extracellular proteins

Kexin Li1,2, Qingji Huo1,2, Nathan H Dimmitt2

  • 1Department of Pharmacology, School of Pharmacy, Harbin Medical University, Harbin, China.

Elife
|March 21, 2023
PubMed

Insights

Mesenchymal stem cell-derived proteins show potential in treating osteosarcoma (OS) by inhibiting bone destruction. Activating specific pathways in stem cells enhanced their tumor-suppressing capabilities, offering a novel therapeutic avenue for this bone cancer.

Area of Science:

  • Oncology
  • Biotechnology
  • Regenerative Medicine

Background:

  • Osteosarcoma (OS) is a primary bone cancer predominantly affecting children and young adults.
  • Standard chemotherapy for OS has limitations, necessitating novel therapeutic strategies.
  • Mesenchymal stem cells (MSCs) and their secreted proteins are being explored for cancer therapy.

Purpose of the Study:

  • To investigate the potential of MSCs-derived proteomes and OS-elevated proteins as a protein-based therapy for osteosarcoma.
  • To evaluate the tumor-suppressing ability of MSCs-conditioned medium (CM) and modified MSCs (iTSCs).
  • To explore the therapeutic efficacy of CM in inhibiting tumor-induced bone destruction in a mouse model.

Main Methods:

  • Collected conditioned medium (CM) from MSCs and activated MSCs (iTSCs) via PKA activation.
  • Administered CM directly and via hydrogel in a mouse model of OS.
  • Analyzed protein enrichment in CM, including calreticulin (CALR) and PCOLCE.
  • Examined interactions between identified proteins (e.g., CALR with CD47, PCOLCE with amyloid precursor protein) and their expression in OS tissues.

Main Results:

  • MSCs-derived CM inhibited tumor-induced bone destruction in a mouse model, with additive effects when combined with cisplatin.
  • Activation of PKA converted MSCs into induced tumor-suppressing cells (iTSCs).
  • Calreticulin (CALR) and PCOLCE were identified as extracellular tumor suppressors in CM, with elevated CALR transcripts in OS tissues.
  • PCOLCE interacted with amyloid precursor protein, a poor prognostic marker in OS.

Conclusions:

  • MSCs-derived proteins, particularly calreticulin and PCOLCE, demonstrate extracellular tumor-suppressing activity against osteosarcoma.
  • A paradoxical strategy utilizing OS transcriptomes for treatment, potentially through engineered MSCs, is supported by these findings.
  • This study highlights the potential of protein-based therapies derived from stem cells and leveraging tumor-specific proteins for osteosarcoma treatment.
Keywords:
CD47MSCPCOLCEcalreticulincancer biologymouseosteosarcomaproteome

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