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Exploring the Link Between PACAP Signalling and Hyaluronic Acid Production in Melanoma Progression.

Tibor Hajdú1, Patrik Kovács1, Éva Katona1

  • 1Department of Anatomy, Histology and Embryology, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, H-4032 Debrecen, Hungary.

International Journal of Molecular Sciences
|December 30, 2025
PubMed
Summary

Pituitary adenylate cyclase-activating polypeptide (PACAP) influences melanoma cell behavior by altering gene expression. PACAP impacts hyaluronan homeostasis, potentially modulating melanoma cell invasiveness.

Keywords:
HASHyalMITFPACAPRHAMMSOX10SOX9hyaluronan

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Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide with known cell-protective effects.
  • PACAP's role in melanoma is debated, with evidence suggesting both anti-invasive and pro-progression effects.

Purpose of the Study:

  • To investigate the signaling targets of PACAP in melanoma cell lines (A2058 and WM35) in vitro.
  • To elucidate the molecular mechanisms underlying PACAP's influence on melanoma progression.

Main Methods:

  • Treatment of melanoma cell lines with PACAP.
  • Analysis of gene expression for key melanocyte differentiation markers (SOX9, SOX10, TYRP1, DCT, MITF).
  • Assessment of hyaluronan (HA) homeostasis markers (HA synthases, RHAMM, Hyal2) and integrin expression (alfaV, beta3).

Main Results:

  • PACAP modulated SOX9 (increased) and SOX10 (decreased) expression, altered MITF localization, and affected TYRP1 (decreased) and DCT (increased) levels.
  • PACAP significantly increased hyaluronan (HA) production and the expression of its related molecules (RHAMM, Hyal2), indicating a role in HA-rich matrix secretion.
  • PACAP did not significantly alter alfaV and beta3 integrin expression.

Conclusions:

  • Exogenous PACAP influences multiple molecular targets within melanoma cells.
  • PACAP's modulation of hyaluronan homeostasis suggests a mechanism by which it can affect melanoma cell invasiveness through tumor matrix composition.