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Inhibition of Granzyme B by PI-9 protects prostate cancer cells from apoptosis

Manisha Ray1, Daniel R Hostetter, Carly R K Loeb

  • 1Graduate Group in Biochemistry and Molecular Biology, University of California, San Francisco, California 94158-2517, USA.

The Prostate
|September 16, 2011
PubMed
Abstract

Insights

Prostate cancer cells can evade immune cell-induced death through the inhibitor of Granzyme B (GrB), known as PI-9. This study shows PI-9 protects cancer cells from apoptosis, suggesting its role in early tumor progression.

Area of Science:

  • Immunology
  • Cancer Biology
  • Molecular Biology

Background:

  • Tumor growth requires evasion of immune surveillance and apoptosis.
  • Granzyme B (GrB) from natural killer cells induces apoptosis.
  • PI-9 is a natural inhibitor of GrB, preventing apoptosis.

Purpose of the Study:

  • To investigate if PI-9 protects prostate cancer cells from apoptosis.
  • To examine PI-9 expression and its role in prostate tumor progression.

Main Methods:

  • Quantified PI-9 expression (qPCR) and GrB activity in prostate cancer cell lines.
  • Overexpressed PI-9 in LNCaP cells and assessed natural killer cell-mediated apoptosis.
  • Examined PI-9 levels in prostate tumor tissue (qPCR and immunohistochemistry).

Main Results:

  • Prostate cancer cell lines expressing PI-9 inhibited GrB activity.
  • Overexpressed PI-9 conferred protection against natural killer cell-induced apoptosis in LNCaP cells.
  • PI-9 was upregulated in low-grade tumors and dysregulated in high-grade tumors, also present in pre-neoplastic lesions.

Conclusions:

  • PI-9 overexpression protects prostate cancer cells from apoptosis, potentially occurring in human tumors.
  • Early prostatic inflammation may trigger PI-9 upregulation.
  • PI-9 upregulation appears critical early in tumor progression, preceding other protective mechanisms.

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