Related Experiment Video

Updated: May 9, 2025

In Vitro Three-Dimensional Sprouting Assay of Angiogenesis Using Mouse Embryonic Stem Cells for Vascular Disease Modeling and Drug Testing
08:04

In Vitro Three-Dimensional Sprouting Assay of Angiogenesis Using Mouse Embryonic Stem Cells for Vascular Disease Modeling and Drug Testing

Published on: May 11, 2021

2.7K

G protein-coupled receptor GPR182 negatively regulates sprouting angiogenesis via modulating CXCL12-CXCR4 axis

Changsheng Chen1, Wei Liu2,3,4, Fang Yuan5,6

  • 1School of Life Sciences, Nantong Laboratory of Development and Diseases, Nantong University, Seyuan Road 9, Nantong, Jiangsu Province, 226019, China. c.chen@ntu.edu.cn.

Angiogenesis
|May 2, 2025
PubMed

Insights

GPR182 negatively regulates tumor angiogenesis by binding CXCL12. Its deficiency promotes tumor growth, suggesting GPR182 as a potential therapeutic target for novel antiangiogenic cancer treatments.

Area of Science:

  • Oncology
  • Molecular Biology
  • Vascular Biology

Background:

  • Angiogenesis is crucial for tumor progression, but antiangiogenic therapies show variable efficacy.
  • GPR182, an endothelial cell receptor, is downregulated in tumors, yet its role in angiogenesis is unclear.
  • Hepatocellular carcinoma (HCC) frequently exhibits reduced GPR182 and increased vascularity.

Purpose of the Study:

  • To define the role of GPR182 in angiogenesis and tumor progression.
  • To investigate the molecular mechanisms underlying GPR182-mediated angiogenesis regulation.
  • To explore GPR182 as a potential therapeutic target for cancer treatment.

Main Methods:

  • Assessed GPR182 expression in HCC and correlated with CD31.
  • Utilized zebrafish models (embryos and HCC) to study Gpr182 deficiency effects on angiogenesis.
  • Examined GPR182-deficient human umbilical vein endothelial cell (HUVEC) behavior.
  • Investigated the molecular interaction of GPR182 with CXCL12 and CXCR4 signaling.
  • Tested the efficacy of CXCR4 blockade (AMD3100) in correcting angiogenic defects.

Main Results:

  • GPR182 expression inversely correlated with CD31 in HCC.
  • Gpr182 deficiency in zebrafish led to enhanced angiogenesis and hypervascularization.
  • GPR182-deficient HUVECs exhibited increased migration and proliferation.
  • GPR182 functions as a decoy receptor for CXCL12, suppressing CXCR4-mediated angiogenesis.
  • AMD3100 treatment reversed abnormal angiogenesis in Gpr182-deficient models.

Conclusions:

  • GPR182 is a novel negative regulator of angiogenesis.
  • GPR182 deficiency promotes tumor vascularization and growth.
  • Targeting GPR182 or its downstream pathways offers a potential new antiangiogenic strategy for cancer therapy.

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