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Published on: February 6, 2019
Expression of proton-sensing G-protein-coupled receptors in selected skin tumors
Anaïs Nassios1, Susanne Wallner1, Sebastian Haferkamp1
1Department of Dermatology, University Medical Center Regensburg, Regensburg, Germany.
Background:
In humans, there are four known proton-sensing G-Protein-coupled receptors (pH-GPCRs): GPR4 (GPR19), TDAG8 (GPR65, T-cell death-associated gene 8), OGR1 (GPR68, ovarian cancer GPCR1) and G2A (GPR132, G2 accumulation protein). They are known to be involved in sensing changes of extracellular proton concentrations in the acidic microenvironment of tumors, which leads to altered cell proliferation, migration, metastasis, immune cell function and inflammation. However, little is known about the expression of pH-GPCRs in the skin and especially skin cancers.
Aim:
We studied the expression of pH-GPCRs in selected skin cancers, that is Merkel cell carcinoma (MCC), dermatofibrosarcoma protuberans (DFSP), atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS).
Methods:
We did immunohistochemistry and immunofluorescence to analyse the expression of GPR4, TDAG8, OGR1 and G2A using paraffin-embedded tissue samples (n = 4, exceptions: PDS GPR4/GPR65 n = 5, AFX GPR132 n = 3) from patients suffering from MCC, DFSP, AFX and PDS.
Results:
(a) GPR4 was expressed on all AFX and PDS specimens. All AFX and MCC showed a positive expression of G2A. All PDS exhibited a strong positive expression of G2A. (b) MCCs neither expressed GPR4 nor TDAG8. All DFSP showed no expression of TDAG8. (c) For any other combination of GPCR and skin disease, we found positive/negative mixed results.
Conclusions:
These are the first results on pH-GPCRs in selected skin cancers. We provide evidence that these GPCRs are differentially expressed on the various types of skin cancers and that they can potentially be addressed as a therapeutic target in extensive disease.
Insights
Proton-sensing G-protein-coupled receptors (pH-GPCRs) are differentially expressed in skin cancers like Merkel cell carcinoma (MCC) and dermatofibrosarcoma protuberans (DFSP). This research highlights their potential as therapeutic targets for extensive skin cancer disease.
Area of Science:
- Oncology
- Molecular Biology
- Dermatology
Background:
- Four proton-sensing G-protein-coupled receptors (pH-GPCRs) are known in humans: GPR4, TDAG8, OGR1, and G2A.
- These receptors sense extracellular proton changes in tumor microenvironments, influencing cancer cell behavior and inflammation.
- Limited information exists on pH-GPCR expression in skin and skin cancers.
Purpose of the Study:
- To investigate the expression patterns of pH-GPCRs in specific skin cancers.
- To explore the potential of pH-GPCRs as therapeutic targets in skin oncology.
Main Methods:
- Immunohistochemistry and immunofluorescence were employed.
- Paraffin-embedded tissue samples from patients with Merkel cell carcinoma (MCC), dermatofibrosarcoma protuberans (DFSP), atypical fibroxanthoma (AFX), and pleomorphic dermal sarcoma (PDS) were analyzed.
- Expression of GPR4, TDAG8, OGR1, and G2A was assessed.
Main Results:
- GPR4 was expressed in all AFX and PDS samples.
- G2A was expressed in all AFX and PDS samples, with strong expression in PDS.
- MCC samples lacked GPR4 and TDAG8 expression, while DFSP samples showed no TDAG8 expression. Other combinations yielded mixed results.
Conclusions:
- This study provides the first data on pH-GPCR expression in selected skin cancers.
- Differential expression of pH-GPCRs was observed across various skin cancer types.
- These findings suggest pH-GPCRs may serve as potential therapeutic targets for advanced skin cancers.
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