We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Elevated serum CXCL16 is an independent predictor of poor survival in ovarian cancer and may reflect pro-metastatic ADAM protease activity.
- Authors
Gooden, M J M; Wiersma, V R; Boerma, A; Leffers, N; Boezen, H M; ten Hoor, K A; Hollema, H; Walenkamp, A M E; Daemen, T; Nijman, H W; Bremer, E
- Abstract
Background:In certain cancers, expression of CXCL16 and its receptor CXCR6 associate with lymphocyte infiltration, possibly aiding anti-tumour immune response. In other cancers, CXCL16 and CXCR6 associate with pro-metastatic activity. In the current study, we aimed to characterise the role of CXCL16, sCXCL16, and CXCR6 in ovarian cancer (OC).Methods:CXCL16/CXCR6 expression was analysed on tissue microarray containing 306 OC patient samples. Pre-treatment serum sCXCL16 was determined in 118 patients using ELISA. In vitro, (primary) OC cells were treated with an ADAM-10/ADAM-17 inhibitor (TAPI-2) and an ADAM-10-specific inhibitor (GI254023x), whereupon CXCL16 levels were evaluated on the cell membrane (immunofluorescent analysis, western blots) and in culture supernatants (ELISA). In addition, cell migration was assessed using scratch assays.Results:sCXCL16 independently predicted for poor survival (hazard ratio=2.28, 95% confidence interval=1.29-4.02, P=0.005), whereas neither CXCL16 nor CXCR6 expression correlated with survival. Further, CXCL16/CXCR6 expression and serum sCXCL16 levels did not associate with lymphocyte infiltration. In vitro inhibition of both ADAM-17 and ADAM-10, but especially the latter, decreased CXCL16 membrane shedding and strongly reduced cell migration of A2780 and cultured primary OC-derived malignant cells.Conclusions:High serum sCXCL16 is a prognostic marker for poor survival of OC patients, possibly reflecting ADAM-10 and ADAM-17 pro-metastatic activity. Therefore, serum sCXCL16 levels may be a pseudomarker that identifies patients with highly metastatic tumours.
- Subjects
OVARIAN cancer patients; SERUM; METASTASIS; PROTEOLYTIC enzymes; ENZYME activation; GENE expression; LYMPHOCYTES; IMMUNE response
- Publication
British Journal of Cancer, 2014, Vol 110, Issue 6, p1535
- ISSN
0007-0920
- Publication type
Article
- DOI
10.1038/bjc.2014.55