Comparative analysis of peritoneum and tumor eicosanoids and pathways in advanced ovarian cancer

Ralph S. Freedman, Ena Wang, Sonia Voiculescu, Rebecca Patenia, Roland L. Bassett, Michael Deavers, Francesco M. Marincola, Peiying Yang, Robert A. Newman

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Purpose: To describe the eicosanoid profile and differentially expressed eicosanoid and arachidonic acid pathway genes in tissues from patients with advanced epithelial ovarian cancer (EOC). Experimental Design: We first employed electrospray tandem mass spectrometry to determine tissue-specific concentrations of the eicosanoids prostaglandin E2 (PGE2), the hydroxyeicosatetraenoic acids (12-HETE and 5-HETE), and leukotriene (LTB4), selected for tumor growth potential, and two other bioactive lipids (15-HETE and 13-HODE) with tumor cell proliferation interference potential. The cellular location of eicosanoid activity was identified by immunofluorescence antibody costaining and confocal microscopy. Differential analysis of eicosanoid and arachidonic pathway genes was done using a previously validated cDNA microarray platform. Tissues used included EOC tumor, tumor-free malignant peritoneum(MP), and benign peritoneum (BP) from patients with benign pelvic disease. Results: (a) Eicosanoid products were detected in tumor, MP, and BP specimens. PGE2 levels were significantly elevated in tumors in an overall comparison with MP or BP (P < 0.001). Combined levels of PGE 2, 12-HETE, 5-HETE, and LTB4 increased progressively from low to high concentrations in BP, MP, and tumors (P = 0.012). Neither 15-HETE nor 13-HODE showed a significant opposite trend toward levels found in BP. (b) Tissue specimens representing common EOC histotypes showed strong coexpressions of cyclooxygenases (COX-1) and prostaglandin E synthases (PGES-1) on tumor cells, whereas intratumoral or peritumoral MO/MA coexpressed COX-1 and COX-2 and PGES-1 and PGES-2, respectively. (c) cDNA microarray analysis of MP, BP, and tumor showed that a number of eicosanoid and arachidonic acid pathway genes were differentially expressed in MP and BP compared with tumor, except for CYP2J2, which was increased in tumors. Conclusions: Elevated levels of eicosanoid metabolites in tumors and differential expression of eicosanoid and arachidonic acid pathway genes in the peritoneum support the involvement of bioactive lipids in the inflammatory tumor environment of EOC.

Original languageEnglish
Pages (from-to)5736-5744
Number of pages9
JournalClinical Cancer Research
Volume13
Issue number19
DOIs
Publication statusPublished - 1 Oct 2007
Externally publishedYes

Fingerprint

Eicosanoids
Peritoneum
Ovarian Neoplasms
Neoplasms
12-Hydroxy-5,8,10,14-eicosatetraenoic Acid
Arachidonic Acid
Cyclooxygenase 1
Leukotriene B4
Oligonucleotide Array Sequence Analysis
Dinoprostone
Genes
Lipids
Hydroxyeicosatetraenoic Acids
Leukotrienes
Microarray Analysis
Tandem Mass Spectrometry
Prostaglandins E
Confocal Microscopy
Fluorescent Antibody Technique

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Freedman, R. S., Wang, E., Voiculescu, S., Patenia, R., Bassett, R. L., Deavers, M., ... Newman, R. A. (2007). Comparative analysis of peritoneum and tumor eicosanoids and pathways in advanced ovarian cancer. Clinical Cancer Research, 13(19), 5736-5744. https://doi.org/10.1158/1078-0432.CCR-07-0583

Comparative analysis of peritoneum and tumor eicosanoids and pathways in advanced ovarian cancer. / Freedman, Ralph S.; Wang, Ena; Voiculescu, Sonia; Patenia, Rebecca; Bassett, Roland L.; Deavers, Michael; Marincola, Francesco M.; Yang, Peiying; Newman, Robert A.

In: Clinical Cancer Research, Vol. 13, No. 19, 01.10.2007, p. 5736-5744.

Research output: Contribution to journalArticle

Freedman, RS, Wang, E, Voiculescu, S, Patenia, R, Bassett, RL, Deavers, M, Marincola, FM, Yang, P & Newman, RA 2007, 'Comparative analysis of peritoneum and tumor eicosanoids and pathways in advanced ovarian cancer', Clinical Cancer Research, vol. 13, no. 19, pp. 5736-5744. https://doi.org/10.1158/1078-0432.CCR-07-0583
Freedman, Ralph S. ; Wang, Ena ; Voiculescu, Sonia ; Patenia, Rebecca ; Bassett, Roland L. ; Deavers, Michael ; Marincola, Francesco M. ; Yang, Peiying ; Newman, Robert A. / Comparative analysis of peritoneum and tumor eicosanoids and pathways in advanced ovarian cancer. In: Clinical Cancer Research. 2007 ; Vol. 13, No. 19. pp. 5736-5744.
@article{7f1f8c52fd10456181386a9819a126f5,
title = "Comparative analysis of peritoneum and tumor eicosanoids and pathways in advanced ovarian cancer",
abstract = "Purpose: To describe the eicosanoid profile and differentially expressed eicosanoid and arachidonic acid pathway genes in tissues from patients with advanced epithelial ovarian cancer (EOC). Experimental Design: We first employed electrospray tandem mass spectrometry to determine tissue-specific concentrations of the eicosanoids prostaglandin E2 (PGE2), the hydroxyeicosatetraenoic acids (12-HETE and 5-HETE), and leukotriene (LTB4), selected for tumor growth potential, and two other bioactive lipids (15-HETE and 13-HODE) with tumor cell proliferation interference potential. The cellular location of eicosanoid activity was identified by immunofluorescence antibody costaining and confocal microscopy. Differential analysis of eicosanoid and arachidonic pathway genes was done using a previously validated cDNA microarray platform. Tissues used included EOC tumor, tumor-free malignant peritoneum(MP), and benign peritoneum (BP) from patients with benign pelvic disease. Results: (a) Eicosanoid products were detected in tumor, MP, and BP specimens. PGE2 levels were significantly elevated in tumors in an overall comparison with MP or BP (P < 0.001). Combined levels of PGE 2, 12-HETE, 5-HETE, and LTB4 increased progressively from low to high concentrations in BP, MP, and tumors (P = 0.012). Neither 15-HETE nor 13-HODE showed a significant opposite trend toward levels found in BP. (b) Tissue specimens representing common EOC histotypes showed strong coexpressions of cyclooxygenases (COX-1) and prostaglandin E synthases (PGES-1) on tumor cells, whereas intratumoral or peritumoral MO/MA coexpressed COX-1 and COX-2 and PGES-1 and PGES-2, respectively. (c) cDNA microarray analysis of MP, BP, and tumor showed that a number of eicosanoid and arachidonic acid pathway genes were differentially expressed in MP and BP compared with tumor, except for CYP2J2, which was increased in tumors. Conclusions: Elevated levels of eicosanoid metabolites in tumors and differential expression of eicosanoid and arachidonic acid pathway genes in the peritoneum support the involvement of bioactive lipids in the inflammatory tumor environment of EOC.",
author = "Freedman, {Ralph S.} and Ena Wang and Sonia Voiculescu and Rebecca Patenia and Bassett, {Roland L.} and Michael Deavers and Marincola, {Francesco M.} and Peiying Yang and Newman, {Robert A.}",
year = "2007",
month = "10",
day = "1",
doi = "10.1158/1078-0432.CCR-07-0583",
language = "English",
volume = "13",
pages = "5736--5744",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "19",

}

TY - JOUR

T1 - Comparative analysis of peritoneum and tumor eicosanoids and pathways in advanced ovarian cancer

AU - Freedman, Ralph S.

AU - Wang, Ena

AU - Voiculescu, Sonia

AU - Patenia, Rebecca

AU - Bassett, Roland L.

AU - Deavers, Michael

AU - Marincola, Francesco M.

AU - Yang, Peiying

AU - Newman, Robert A.

PY - 2007/10/1

Y1 - 2007/10/1

N2 - Purpose: To describe the eicosanoid profile and differentially expressed eicosanoid and arachidonic acid pathway genes in tissues from patients with advanced epithelial ovarian cancer (EOC). Experimental Design: We first employed electrospray tandem mass spectrometry to determine tissue-specific concentrations of the eicosanoids prostaglandin E2 (PGE2), the hydroxyeicosatetraenoic acids (12-HETE and 5-HETE), and leukotriene (LTB4), selected for tumor growth potential, and two other bioactive lipids (15-HETE and 13-HODE) with tumor cell proliferation interference potential. The cellular location of eicosanoid activity was identified by immunofluorescence antibody costaining and confocal microscopy. Differential analysis of eicosanoid and arachidonic pathway genes was done using a previously validated cDNA microarray platform. Tissues used included EOC tumor, tumor-free malignant peritoneum(MP), and benign peritoneum (BP) from patients with benign pelvic disease. Results: (a) Eicosanoid products were detected in tumor, MP, and BP specimens. PGE2 levels were significantly elevated in tumors in an overall comparison with MP or BP (P < 0.001). Combined levels of PGE 2, 12-HETE, 5-HETE, and LTB4 increased progressively from low to high concentrations in BP, MP, and tumors (P = 0.012). Neither 15-HETE nor 13-HODE showed a significant opposite trend toward levels found in BP. (b) Tissue specimens representing common EOC histotypes showed strong coexpressions of cyclooxygenases (COX-1) and prostaglandin E synthases (PGES-1) on tumor cells, whereas intratumoral or peritumoral MO/MA coexpressed COX-1 and COX-2 and PGES-1 and PGES-2, respectively. (c) cDNA microarray analysis of MP, BP, and tumor showed that a number of eicosanoid and arachidonic acid pathway genes were differentially expressed in MP and BP compared with tumor, except for CYP2J2, which was increased in tumors. Conclusions: Elevated levels of eicosanoid metabolites in tumors and differential expression of eicosanoid and arachidonic acid pathway genes in the peritoneum support the involvement of bioactive lipids in the inflammatory tumor environment of EOC.

AB - Purpose: To describe the eicosanoid profile and differentially expressed eicosanoid and arachidonic acid pathway genes in tissues from patients with advanced epithelial ovarian cancer (EOC). Experimental Design: We first employed electrospray tandem mass spectrometry to determine tissue-specific concentrations of the eicosanoids prostaglandin E2 (PGE2), the hydroxyeicosatetraenoic acids (12-HETE and 5-HETE), and leukotriene (LTB4), selected for tumor growth potential, and two other bioactive lipids (15-HETE and 13-HODE) with tumor cell proliferation interference potential. The cellular location of eicosanoid activity was identified by immunofluorescence antibody costaining and confocal microscopy. Differential analysis of eicosanoid and arachidonic pathway genes was done using a previously validated cDNA microarray platform. Tissues used included EOC tumor, tumor-free malignant peritoneum(MP), and benign peritoneum (BP) from patients with benign pelvic disease. Results: (a) Eicosanoid products were detected in tumor, MP, and BP specimens. PGE2 levels were significantly elevated in tumors in an overall comparison with MP or BP (P < 0.001). Combined levels of PGE 2, 12-HETE, 5-HETE, and LTB4 increased progressively from low to high concentrations in BP, MP, and tumors (P = 0.012). Neither 15-HETE nor 13-HODE showed a significant opposite trend toward levels found in BP. (b) Tissue specimens representing common EOC histotypes showed strong coexpressions of cyclooxygenases (COX-1) and prostaglandin E synthases (PGES-1) on tumor cells, whereas intratumoral or peritumoral MO/MA coexpressed COX-1 and COX-2 and PGES-1 and PGES-2, respectively. (c) cDNA microarray analysis of MP, BP, and tumor showed that a number of eicosanoid and arachidonic acid pathway genes were differentially expressed in MP and BP compared with tumor, except for CYP2J2, which was increased in tumors. Conclusions: Elevated levels of eicosanoid metabolites in tumors and differential expression of eicosanoid and arachidonic acid pathway genes in the peritoneum support the involvement of bioactive lipids in the inflammatory tumor environment of EOC.

UR - http://www.scopus.com/inward/record.url?scp=35348876122&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=35348876122&partnerID=8YFLogxK

U2 - 10.1158/1078-0432.CCR-07-0583

DO - 10.1158/1078-0432.CCR-07-0583

M3 - Article

VL - 13

SP - 5736

EP - 5744

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 19

ER -