14-3-3 zeta protein secreted by tumor associated monocytes/macrophages from ascites of epithelial ovarian cancer patients.


Journal Article

Tumor associated monocytes/macrophages (MO/MA) are known contributors to the immune-inflammatory cell environment of advanced epithelial ovarian carcinoma (EOC). The secreted proteome of ascitic MO/MA was examined as an aid to the discovery of novel proteins in EOC that are likely to have biological relevance in the inflammatory pathways of EOC. Ascitic fluid MO/MA were isolated from EOC patients, grown short-term in serum-free media. MO/MA supernatants were analyzed for secreted proteins by HPLC fractionation followed by LC-tandem mass spectrometric analysis. The 14-3-3 zeta adaptor protein was identified in supernatants of three of three EOC patients but not in supernatants of buffy coat monocytes isolated from normal donors or the established monocyte cell line THP1. Moreover, 14-3-3 zeta was identified in ascitic fluids in eight of eight chemotherapy-naïve patients by both immunoblot and mass spectrometric analysis. Immunofluorescent staining for 14-3-3 zeta demonstrated expression of the protein on ascitic and peritumoral macrophages in EOC patients. 14-3-3 zeta was also expressed on endothelial cells in the peritumoral stroma and partially on tumor cells. Uptake of 14-3-3 zeta was observed in EOC cell lines co-cultured with the recombinant protein expressed in E. coli. It is demonstrated for the first time that the important adaptor protein 14-3-3 zeta is common to the secretome of ascitic MO/MA and the ascites of advanced EOC patients.

Full Text

Cited Authors

  • Kobayashi, R; Deavers, M; Patenia, R; Rice-Stitt, T; Halbe, J; Gallardo, S; Freedman, RS

Published Date

  • February 2009

Published In

Volume / Issue

  • 58 / 2

Start / End Page

  • 247 - 258

PubMed ID

  • 18618111

Pubmed Central ID

  • 18618111

Electronic International Standard Serial Number (EISSN)

  • 1432-0851

International Standard Serial Number (ISSN)

  • 0340-7004

Digital Object Identifier (DOI)

  • 10.1007/s00262-008-0549-7


  • eng