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The inflammatory cytokine tumor necrosis factor-alpha generates an autocrine tumor-promoting network in epithelial ovarian cancer cells.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Kulbe, Hagen Thompson, Richard G. Wilson, Julia L. Robinson, Stephen Cory Hagemann, Thorsten Fatah, R. Eep Saefulloh Gould, David Ayhan, Ayse Balkwill, Frances R. |
| Copyright Year | 2007 |
| 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 TNF-alpha, 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. |
| File Format | PDF HTM / HTML |
| DOI | 10.1158/0008-5472.CAN-06-2941 |
| PubMed reference number | 17234767 |
| Journal | Medline |
| Volume Number | 67 |
| Issue Number | 2 |
| Alternate Webpage(s) | http://cancerres.aacrjournals.org/content/canres/67/2/585.full.pdf |
| Alternate Webpage(s) | https://doi.org/10.1158/0008-5472.CAN-06-2941 |
| Journal | Cancer research |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
