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Acetylcholine receptor expression in Merkel cell carcinoma
Jeremy W Bowers1, Scott M Schlauder, Kenneth B Calder
1Department of Pathology and Cell Biology, University of South Florida College of Medicine, Tampa, FL 33612, USA. jbowers@health.usf.edu
The American Journal of Dermatopathology
|July 23, 2008
Summary
Merkel cell carcinoma (MCC) uniformly expresses M3 and M5 muscarinic receptors, but not beta 2 nicotinic receptors. These findings suggest potential therapeutic targets for MCC, a neuroendocrine tumor.
Area of Science:
- Oncology
- Neuroscience
- Dermatopathology
Background:
- Neurocrest-derived tissues express muscarinic and nicotinic acetylcholine receptors (mAChR and nAChR).
- These receptors are crucial for neurocrest cell development and migration.
- Recent studies show expression in melanoma and neuroendocrine tumors, prompting investigation in Merkel cell carcinoma (MCC).
Purpose of the Study:
- To investigate the immunohistochemical expression of mAChR and nAChR in primary cutaneous MCC.
- To explore the potential role of these receptors in MCC pathogenesis and as therapeutic targets.
Main Methods:
- Retrieved fifteen archival cases of primary non-metastatic cutaneous MCC.
- Utilized immunohistochemistry to evaluate M3, M5 mAChR, and beta 2 nAChR expression.
- Confirmed all cases prior to study by a board-certified dermatopathologist.
Main Results:
- All fifteen MCC cases showed diffuse positive staining for M3 and M5 mAChR.
- No immunohistochemical staining for beta 2 nAChR was observed in any case.
- MCC uniformly expresses M3 and M5 receptors, suggesting a potential role in tumor biology.
Conclusions:
- Merkel cell carcinoma (MCC) consistently expresses M3 and M5 muscarinic receptors.
- The absence of beta 2 nAChR suggests specific receptor involvement in MCC.
- M3 and M5 receptors, linked to cell proliferation and migration, represent potential therapeutic targets for MCC.
Related Concept Videos
Cholinergic Receptors: Muscarinic
The pharmacological actions of acetylcholine are elicited via its binding to two families of cholinergic receptors or cholinoceptors, namely, muscarinic and nicotinic receptors. Muscarinic receptors are G protein-coupled receptors and have five subtypes, M1–M5. All mAChR subtypes are activated by acetylcholine and blocked by the antagonist, atropine.
The subtypes M1, M3, and M5 couple with the Gq subunit and activate the phospholipase C (PLC) activity, mobilizing intracellular Ca2+. Activation...
The subtypes M1, M3, and M5 couple with the Gq subunit and activate the phospholipase C (PLC) activity, mobilizing intracellular Ca2+. Activation...
Cholinergic Receptors: Nicotinic
Nicotinic receptors are ligand-gated ion channels that are activated by acetylcholine and nicotine. Upon activation, they cause a rapid increase in the permeability of cells to K+, Na+, and Ca2+, followed by depolarization and excitation. They are in the autonomic ganglia, skeletal neuromuscular junction, CNS, and adrenal medulla.
There are two types of nicotinic receptors: neuromuscular (NM/NM/N1) and neuronal (NN/NN/N2). The two families differ based on their location and selectivity to...
There are two types of nicotinic receptors: neuromuscular (NM/NM/N1) and neuronal (NN/NN/N2). The two families differ based on their location and selectivity to...
