dc.contributor.author | Kulbe, Hagen | |
dc.contributor.author | Thompson, Richard | |
dc.contributor.author | Wilson, Julia L. | |
dc.contributor.author | Robinson, Stephen | |
dc.contributor.author | Hagemann, Thorsten | |
dc.contributor.author | Fatah, Rewas | |
dc.contributor.author | Gould, David | |
dc.contributor.author | Ayhan, Ayse | |
dc.contributor.author | Balkwill, Frances | |
dc.date.accessioned | 2019-12-12T06:46:44Z | |
dc.date.available | 2019-12-12T06:46:44Z | |
dc.date.issued | 2007 | |
dc.identifier.issn | 0008-5472 | |
dc.identifier.uri | https://doi.org/10.1158/0008-5472.CAN-06-2941 | |
dc.identifier.uri | http://hdl.handle.net/11655/17010 | |
dc.description.abstract | Constitutive expression of the inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) is characteristic of malignant ovarian surface epithelium. We investigated the hypothesis that this autocrine action of TNF-alpha generates and sustains a network of other mediators that promote peritoneal cancer growth and spread. When compared with two ovarian cancer cell lines that did not make TNT-a., constitutive production of TNF-alpha was associated with greater release of the chemokines CCL2 and CXCL12, the cytokines interleukin-6 (IL-6) and macrophage migration-inhibitory factor (MIF), and the angiogenic factor vascular endothelial growth factor (VEGF). TNF-alpha production was associated also with increased peritoneal dissemination when the ovarian cancer cells were xenografted. We next used RNA interference to generate stable knockdown of TNF-alpha in ovarian cancer cells. Production of CCL2, CXCL12, VEGF, IL-6, and MIF was decreased significantly in these cells compared with wild-type or mock-transfected cells, but in vitro growth rates were unaltered. Tumor growth and dissemination in vivo were significantly reduced when stable knockdown of TNF-alpha was achieved. Tumors derived from TNF-alpha knockdown cells were noninvasive and well circumscribed and showed high levels of apoptosis, even in the smallest deposits. This was reflected in reduced vascularization of TNF-alpha knockdown tumors. Furthermore, culture supernatants from such cells failed to stimulate endothelial cell growth in vitro. We conclude that autocrine production of TNF-alpha by ovarian cancer cells stimulates a constitutive network of other cytokines, angiogenic factors, and chemokines that may act in an autocrine/paracrine manner to promote colonization of the peritoneum and neovascularization of developing tumor deposits. | |
dc.language.iso | en | |
dc.publisher | Amer Assoc Cancer Research | |
dc.relation.isversionof | 10.1158/0008-5472.CAN-06-2941 | |
dc.rights | info:eu-repo/semantics/openAccess | |
dc.subject | Oncology | |
dc.title | The Inflammatory Cytokine Tumor Necrosis Factor-Alpha Generates An Autocrine Tumor-Promoting Network In Epithelial Ovarian Cancer Cells | |
dc.type | info:eu-repo/semantics/article | |
dc.type | info:eu-repo/semantics/publishedVersion | |
dc.relation.journal | Cancer Research | |
dc.contributor.department | Tıbbi Patoloji | |
dc.identifier.volume | 67 | |
dc.identifier.issue | 2 | |
dc.identifier.startpage | 585 | |
dc.identifier.endpage | 592 | |
dc.description.index | WoS | |