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Updated: Jun 13, 2026

A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
Published on: February 20, 2018
Vascular CXCR4 expression - a novel antiangiogenic target in gastric cancer?
Barbara Ingold1, Eva Simon, Ute Ungethüm
1Institute of Pathology Campus Mitte, Charité University Hospital, Berlin, Germany.
Background:
G-protein-coupled receptors (GPCRs) are prime candidates for novel cancer prevention and treatment strategies. We searched for differentially expressed GPCRs in node positive gastric carcinomas.
Methodology/Principal Findings:
Differential expression of GPCRs in three node positive vs. three node negative intestinal type gastric carcinomas was analyzed by gene array technology. The candidate genes CXCL12 and its receptor CXCR4 were validated by real-time reverse-transcription polymerase chain reaction in an independent set of 37 gastric carcinomas. Translation was studied by immunohistochemistry in 347 gastric carcinomas using tissue microarrays as well as in 61 matching lymph node metastases. Protein expression was correlated with clinicopathological patient characteristics and survival. 52 GPCRs and GPCR-related genes were up- or down-regulated in node positive gastric cancer, including CXCL12. Differential expression of CXCL12 was confirmed by RT-PCR and correlated with local tumour growth. CXCL12 immunopositivity was negatively associated with distant metastases and tumour grade. Only 17% of gastric carcinomas showed CXCR4 immunopositive tumour cells, which was associated with higher local tumour extent. 29% of gastric carcinomas showed CXCR4 positive tumour microvessels. Vascular CXCR4 expression was significantly associated with higher local tumour extent as well as higher UICC-stages. When expressing both, CXCL12 in tumour cells and CXCR4 in tumour microvessels, these tumours also were highly significantly associated with higher T- and UICC-stages. Three lymph node metastases revealed vascular CXCR4 expression while tumour cells completely lacked CXCR4 in all cases. The expression of CXCL12 and CXCR4 had no impact on patient survival.
Conclusions/Significance:
Our results substantiate the significance of GPCRs on the biology of gastric carcinomas and provide evidence that the CXCL12-CXCR4 pathway might be a novel promising antiangiogenic target for the treatment of gastric carcinomas.
Insights
This study found that the CXCL12-CXCR4 pathway is involved in gastric cancer progression and may be a target for anti-angiogenic therapy. Further research is needed to explore its therapeutic potential in gastric carcinomas.
Area of Science:
- Oncology
- Molecular Biology
- Gastroenterology
Background:
- G-protein-coupled receptors (GPCRs) are crucial in cancer development and present therapeutic targets.
- Gastric carcinomas, particularly node-positive cases, require further investigation for differentially expressed GPCRs.
Purpose of the Study:
- To identify and analyze differentially expressed GPCRs in node-positive gastric carcinomas.
- To investigate the role of the CXCL12-CXCR4 pathway in gastric cancer biology and its potential as an antiangiogenic target.
Main Methods:
- Gene array technology was used to analyze GPCR expression in gastric carcinomas.
- Real-time RT-PCR validated CXCL12 and CXCR4 expression in an independent cohort.
- Immunohistochemistry assessed protein expression in tumor tissues and lymph node metastases, correlating with clinicopathological data and survival.
Main Results:
- 52 GPCRs were differentially expressed in node-positive gastric cancer, including CXCL12.
- CXCL12 expression correlated with local tumor growth but not survival.
- Vascular CXCR4 expression was linked to increased local tumor extent and advanced UICC stages.
Conclusions:
- GPCRs play a significant role in gastric carcinoma biology.
- The CXCL12-CXCR4 pathway shows promise as a novel antiangiogenic therapeutic target for gastric carcinomas.
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