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LRP8 activates STAT3 to induce PD-L1 expression in osteosarcoma.

Shiqin Zheng1, Yuxi Wei1, Yu Jiang1

  • 1Department of Osteoarthrosis, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, China.

Tumori
|October 15, 2020
PubMed
Summary

Low-density lipoprotein receptor-related protein 8 (LRP8) promotes osteosarcoma progression by activating the STAT3/PD-L1 pathway, suggesting LRP8 as a potential therapeutic target for osteosarcoma treatment.

Keywords:
LRP8OsteosarcomaPD-L1STAT3immune checkpoint

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Area of Science:

  • Immunology
  • Oncology
  • Molecular Biology

Background:

  • Programmed death-ligand 1 (PD-L1) targeting shows promise for osteosarcoma treatment.
  • PD-L1 expression is regulated by various factors, with its role in osteosarcoma pathogenesis under investigation.
  • Low-density lipoprotein receptor-related protein 8 (LRP8) influences osteoblast differentiation, but its contribution to osteosarcoma is not well understood.

Purpose of the Study:

  • To investigate the novel LRP8/signal transducer and activator of transcription 3 (STAT3)/PD-L1 regulatory network in osteosarcoma.
  • To determine the role of LRP8 in osteosarcoma pathogenesis and its potential as a therapeutic target.

Main Methods:

  • Quantitative analysis of LRP8, STAT3, and PD-L1 expression in osteosarcoma and normal tissues.
  • In vitro studies using osteosarcoma cell lines to assess LRP8's effects on STAT3 and PD-L1.
  • Co-culture systems with Jurkat cells to evaluate LRP8-mediated immunosuppression and the impact of LRP8 inhibition.

Main Results:

  • LRP8 is overexpressed in osteosarcoma and correlates with phospho-STAT3 (p-STAT3) levels.
  • LRP8 enhances p-STAT3 levels, promotes STAT3 nuclear translocation, and increases PD-L1 expression via STAT3 activation.
  • LRP8 overexpression impairs Jurkat cell function and induces apoptosis; blocking LRP8 inhibits osteosarcoma cell proliferation and induces apoptosis.

Conclusions:

  • A novel LRP8/STAT3/PD-L1 regulatory network is identified in osteosarcoma.
  • LRP8 plays a significant role in osteosarcoma progression and immunosuppression.
  • LRP8 represents a promising therapeutic target for osteosarcoma.