Secretory phospholipase A2-IIa is involved in prostate cancer progression and may potentially serve as a biomarker for prostate cancer.

Abstract

The majority of prostate cancers are indolent, whereas a significant portion of patients will require systemic treatment during the course of their disease. To date, only high Gleason scores are best associated with a poor prognosis in prostate cancer. No validated serum biomarker has been identified with prognostic power. Previous studies showed that secretory phospholipase A2-IIa (sPLA2-IIa) is overexpressed in almost all human prostate cancer specimens and its elevated levels are correlated with high tumor grade. Here, we found that sPLA2-IIa is overexpressed in androgen-independent prostate cancer LNCaP-AI cells relative to their androgen-dependent LNCaP cell counterparts. LNCaP-AI cells also secrete significantly higher levels of sPLA2-IIa. Blocking sPLA2-IIa function compromises androgen-independent cell growth. Inhibition of the ligand-induced signaling output of the HER network, by blocking PI3K-Akt signaling and the nuclear factor-kappaB (NF-κB)-mediated pathway, compromises both sPLA2-IIa protein expression and secretion, as a result of downregulation of sPLA2-IIa promoter activity. More importantly, we demonstrated elevated serum sPLA2-IIa levels in prostate cancer patients. High serum sPLA2-IIa levels are associated significantly with high Gleason score and advanced disease stage. Increased sPLA2-IIa expression was confirmed in prostate cancer cells, but not in normal epithelium and stroma by immunohistochemistry analysis. We showed that elevated signaling of the HER/HER2-PI3K-Akt-NF-κB pathway contributes to sPLA2-IIa overexpression and secretion by prostate cancer cells. Given that sPLA2-IIa overexpression is associated with prostate development and progression, serum sPLA2-IIa may serve as a prognostic biomarker for prostate cancer and a potential surrogate prostate biomarker indicative of tumor burden.

• Authors: Zhongyun Dong, Yin Liu, Kieran F Scott, Linda Levin, Krishnanath Gaitonde, R Bruce Bracken, Barbara Burke, Qihui Jim Zhai, Jiang Wang, Leslie Oleksowicz, Shan Lu
• Journal: Carcinogenesis (Carcinogenesis) Vol. 31 Issue 11 Pg. 1948-55 (Nov 2010) ISSN: 1460-2180 [Electronic] England
• PMID: 20837598 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• NF-kappa B
• RNA, Messenger
• RNA, Small Interfering
• Phosphatidylinositol 3-Kinases
• ERBB2 protein, human
• Receptor, ErbB-2
• Proto-Oncogene Proteins c-akt
• Group II Phospholipases A2

Topics

• Biomarkers, Tumor (blood)
• Blotting, Western
• Cell Proliferation
• Cells, Cultured
• Disease Progression
• Enzyme-Linked Immunosorbent Assay
• Group II Phospholipases A2 (physiology)
• Humans
• Male
• NF-kappa B (metabolism)
• Neoplasm Staging
• Neoplasms, Hormone-Dependent (blood, genetics, pathology)
• Phosphatidylinositol 3-Kinases (metabolism)
• Prostatic Neoplasms (blood, genetics, pathology)
• Proto-Oncogene Proteins c-akt (metabolism)
• RNA, Messenger (genetics)
• RNA, Small Interfering (pharmacology)
• Receptor, ErbB-2 (metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Signal Transduction