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A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
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Elevated phospholipase D activity in androgen-insensitive prostate cancer cells promotes both survival and metastatic

Matthew Utter1, Sohag Chakraborty1, Limor Goren2

  • 1Department of Biological Sciences, Hunter College of the City University of New York, New York, NY, 10065, USA; Biochemistry Program, Graduate Center of the City University of New York, New York, NY, 10016, USA.

Cancer Letters
|March 11, 2018
PubMed

Insights

Androgen-insensitive prostate cancer cells show higher phospholipase D (PLD) activity, which promotes survival and metastasis. Suppressing PLD halts cancer cell migration and invasion, suggesting metastasis is an early event in prostate cancer progression.

Area of Science:

  • Oncology
  • Cell Biology
  • Biochemistry

Background:

  • Prostate cancer growth is often driven by hormones, necessitating androgen receptor blockade.
  • Androgen deprivation therapy can lead to androgen-insensitive cells, associated with metastasis and poor patient survival.
  • Phospholipase D (PLD) activity is implicated in cancer cell survival across various human cancer types.

Purpose of the Study:

  • To investigate the role of PLD activity in androgen-insensitive prostate cancer.
  • To determine if PLD inhibition affects the survival and metastatic potential of these cells.

Main Methods:

  • Comparison of PLD activity in androgen-sensitive versus androgen-insensitive prostate cancer cells.
  • Suppression of PLD activity in androgen-insensitive prostate cancer cell lines.
  • Assessment of cell migration and invasion through Matrigel™.

Main Results:

  • Androgen-insensitive prostate cancer cells exhibit significantly elevated PLD activity compared to androgen-sensitive cells.
  • Suppression of PLD activity induced apoptotic cell death in prostate cancer cells.
  • Inhibition of elevated PLD activity in androgen-resistant cells blocked their migration and invasion capabilities.

Conclusions:

  • Elevated PLD activity is a characteristic of androgen-insensitive prostate cancer and is linked to both cell survival and metastatic phenotypes.
  • The findings suggest that metastasis may occur earlier in prostate cancer than previously assumed.
  • Targeting PLD activity presents a potential therapeutic strategy for advanced prostate cancer and may inform improved screening approaches.
Keywords:
ApoptosisMetastasisProstate cancerProstate cancer phospholipase DSurvival

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