This melanogenic function of UVRAG is controlled by the melanocyte-specific transcription factor MITF as a downstream effector of the α-melanocyte-stimulating hormone (α-MSH)-cAMP signaling in the suntan response, which is compromised in BRAF mutant melanoma.
Radiolabeled α-melanocyte-stimulating hormone (α-MSH) derivatives have a high potential for diagnosis and treatment of melanoma, because of high specificity and binding affinity to the melanocortin-1 receptor (MC1R).
Herein, we sought to establish a simple preparation method for an <sup>18</sup>F-labeled α-MSH analog using Al<sup>18</sup>F, and we examined its potential for the early detection of melanoma.
αMSH peptide sequences, evaluated for conjugation to the PEG-Cy5-C' dot nanoparticles, bound to MC1-R with high affinity and targeted melanoma in syngenetic and xenografted melanoma mouse models.
These results highlight the potential of using radiolabeled αMSH analogues in clinical applications for molecular imaging and radionuclide therapy of melanoma.
MC1R, a G-protein coupled receptor with high affinity for alpha-melanocyte stimulating hormone (αMSH), modulates pigment production in melanocytes from many species and is associated with human melanoma risk.
Radionuclide Targeting: α-Melanocyte-stimulating hormone (α-MSH) is the most prominent peptide for targeting of melanoma tumors via the G protein-coupled melanocortin-1 receptor that is (over-)expressed by melanoma cells and melanocytes.
[Leu<sup>3</sup>, Leu<sup>7</sup>, Phe<sup>8</sup>]-γ-MSH-NH<sub>2</sub> is ideal for inducing short-term skin pigmentation without sun for melanoma prevention.
Linear and cyclic analogues of the α-melanocyte stimulating hormone (α-MSH) targeting the human melanocortin receptor 1 (MC1R) are of pharmacological interest for detecting and treating melanoma.
The importance of the MC1R in reducing UV-induced genotoxicity in melanocytes led us to design small peptide analogs of the physiological MC1R agonist α-melanocortin (α-melanocyte stimulating hormone; α-MSH) for the goal of utilizing them for melanoma chemoprevention.
Our previous studies have indicated that POMC gene delivery inhibited the progression and metastasis of B16-F10 melanoma via the α- melanocyte-stimulating hormone/melanortin-1 receptor (MC-1R) pathway.
In summary, systemic POMC therapy suppresses melanoma growth via induction of melanogenic differentiation and angiogenesis blockade, thereby demonstrating its potential as a novel treatment modality for melanoma.
Furthermore, the relevance of alpha-melanocyte-stimulating hormone-mediated signaling for the induction of cytotoxicity was assessed in CD8(+) T cells from melanoma patients with functional and nonfunctional melanocortin-1 receptors.
Syndecan-2 expression was enhanced by fibroblast growth factor-2, which is known to stimulate melanoma cell migration; however, alpha-melanocyte-stimulating hormone decreased syndecan-2 expression and melanoma cell migration and invasion in a melanin synthesis-independent manner.
An (18)F-labeled linear alpha-MSH peptide ((18)F-FB-Ac-Nle-Asp-His-d-Phe-Arg-Trp-Gly-Lys-NH(2) [NAPamide]) shows promising melanoma imaging properties but with only moderate tumor uptake and retention.
In melanocytes and melanoma cells alpha-melanocyte stimulating hormone (alpha-MSH), via the cAMP pathway, elicits a large array of biological responses that control melanocyte differentiation and influence melanoma development or susceptibility.
However, melanoma cells synthesize and release alpha-melanocyte stimulating hormone (alphaMSH, the ligand for MC1R), therefore MC1R variants could alter the autocrine effects of alphaMSH on melanoma cell behaviour, thereby affecting early melanoma development and progression via non-pigmentary mechanisms.