Serotonin and Dopamine Receptor Expression in Solid Tumours Including Rare Cancers

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Preclinical data suggest serotonin stimulates and dopamine inhibits tumor growth and angiogenesis.
• Limited information exists on serotonin and dopamine receptor (5-HTR and DRD) expression in human cancers.

Purpose of the Study:

• To screen a large set of human tumors for mRNA overexpression of 5-HTR1B, 5-HTR2B, DRD1, and DRD2.
• To analyze the protein expression and localization of these receptors in various tumor types.

Main Methods:

• Functional genomic mRNA (FGmRNA) profiling of 11,756 tumor samples across 43 types against 3,520 normal tissues.
• Immunohistochemistry to assess protein expression and location of 5-HTR1B, 5-HTR2B, DRD1, and DRD2.

Main Results:

• 5-HTR2B mRNA overexpression was frequent, notably in uveal melanomas (56%).
• mRNA overexpression of 5-HTR1B, DRD1, and DRD2 was observed in rare cancers like nasopharyngeal carcinoma, ependymoma, synovial sarcoma, and astrocytoma.
• High 5-HTR2B protein expression was found on tumor cells and endothelial cells in multiple cancer types. High DRD2 expression was seen in pheochromocytomas, and DRD1 expression varied across tumors.

Conclusions:

• 5-HTR1B, 5-HTR2B, DRD1, and DRD2 receptors show mRNA overexpression in a wide range of common and rare human cancers.
• 5-HTR2B protein is frequently highly expressed in human cancers, especially on endothelial cells.
• These findings highlight 5-HTR2B as a promising target for further investigation in cancer therapy.