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Dopamine receptor type 2 (DRD2) inhibits migration and invasion of human tumorous pituitary cells through

E Peverelli1, E Giardino1, D Treppiedi1

  • 1Endocrine Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.

Cancer Letters
|August 14, 2016
PubMed

Insights

Dopamine receptor 2 (DRD2) agonists reduce pituitary tumor invasion by increasing inactive cofilin. Cofilin activation promotes tumor invasiveness, suggesting it may be a biomarker for pituitary tumors.

Area of Science:

  • Endocrinology
  • Oncology
  • Cell Biology

Background:

  • Non-functioning pituitary tumors (NFPTs) often exhibit local invasiveness.
  • Dopamine receptor 2 (DRD2) agonists are the sole medical treatment shown to shrink some NFPTs.
  • Tumor invasion involves cytoskeleton rearrangements regulated by the cofilin pathway.

Purpose of the Study:

  • To investigate the impact of DRD2 agonists on NFPT cell migration and invasion.
  • To elucidate the molecular mechanisms underlying DRD2 agonist effects on pituitary tumor cells.

Main Methods:

  • Treatment of NFPT cells with DRD2 agonists.
  • Assessment of cell migration and invasion.
  • Analysis of cofilin phosphorylation and activity.
  • Investigation using ROCK inhibitors and cofilin mutants.
  • Comparison of cofilin levels in invasive versus non-invasive tumors.

Main Results:

  • DRD2 agonist treatment significantly reduced NFPT cell migration and invasion.
  • DRD2 agonists increased Ser3-phosphorylated inactive cofilin (P-cofilin) levels.
  • Inhibition of ROCK abolished the effects of DRD2 agonists.
  • Overexpression of active cofilin enhanced cell migration, while phosphomimetic mutants did not.
  • Invasive tumors exhibited lower P-cofilin levels compared to non-invasive tumors.

Conclusions:

  • Pituitary tumor invasiveness is promoted by cofilin pathway activation.
  • DRD2 agonists inhibit invasion by increasing inactive cofilin.
  • Cofilin phosphorylation status may serve as a novel biomarker for pituitary tumor invasiveness.
Keywords:
CofilinDopamine receptor type 2InvasionMigrationPituitary tumor

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