Up-regulation of the inflammatory-reparative phenotype in human prostate carcinoma

Prostate. 2009 Aug 1;69(11):1245-55. doi: 10.1002/pros.20966.

Abstract

Background: Recent studies have underlined the role of tumor cells in the endogenous synthesis of pro-inflammatory molecules. We tested whether malignant progression in prostate cancer was associated with the activation of a phenotype typical of the innate immune system.

Methods: The expression of a set of molecules involved in tissue inflammation and repair was measured by real-time PCR and Western blot analysis in prostate samples in the absence or slight presence of a detectable leukocyte infiltrate. Whole tumor and non-tumor samples were analyzed in addition to laser-capture microdissected tumor and host epithelium. Receptor for advanced glycation end products, purine receptor, inducible enzymes cyclooxygenase-2 and nitric oxide synthase-2, pentraxin-3 and growth-survival factor receptors such as epithelial growth factor and estrogen alpha and beta receptors were all studied.

Results: A global survey approach showed an up-regulation in tumor samples of all of the studied genes, with the exception of ERbeta. A laser-capture microdissection approach highlighted over-expression of pro-inflammatory molecules in each tumor sample examined. Nuclear translocation of nuclear factor-kB subunit p65 was observed in tumor tissues.

Conclusions: These data support the evidence that molecules typical of the innate immune system, similar to that of activated leukocytes, are produced by prostate epithelial cells and that their expression is up-regulated in malignant cells. We suggest that the observed pro-inflammatory and repair process activation may represent an important molecular mechanism in the progression of prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biopsy
  • C-Reactive Protein / genetics
  • C-Reactive Protein / metabolism
  • Case-Control Studies
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • DNA Repair / genetics*
  • DNA, Neoplasm / genetics
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism
  • Estrogen Receptor alpha / genetics
  • Estrogen Receptor alpha / metabolism
  • Estrogen Receptor beta / genetics
  • Estrogen Receptor beta / metabolism
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • Inflammation / genetics*
  • Male
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism
  • Phenotype*
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptor for Advanced Glycation End Products / genetics
  • Receptor for Advanced Glycation End Products / metabolism
  • Receptors, Purinergic P2 / genetics
  • Receptors, Purinergic P2 / metabolism
  • Receptors, Purinergic P2X7
  • Serum Amyloid P-Component / genetics
  • Serum Amyloid P-Component / metabolism
  • Signal Transduction / genetics
  • Up-Regulation / genetics*

Substances

  • DNA, Neoplasm
  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • P2RX7 protein, human
  • RNA, Messenger
  • Receptor for Advanced Glycation End Products
  • Receptors, Purinergic P2
  • Receptors, Purinergic P2X7
  • Serum Amyloid P-Component
  • PTX3 protein
  • C-Reactive Protein
  • Nitric Oxide Synthase Type II
  • Cyclooxygenase 2
  • EGFR protein, human
  • ErbB Receptors