The DOI matches its Crossref record; 29 of the 29 references it cites were found in a registry or an index.
The Inflammatory Cytokine Tumor Necrosis Factor-α Generates an Autocrine Tumor-Promoting Network in Epithelial Ovarian Cancer Cells
Open accessAbstract
Constitutive expression of the inflammatory cytokine tumor necrosis factor-α (TNF-α) is characteristic of malignant ovarian surface epithelium. We investigated the hypothesis that this autocrine action of TNF-α 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-α, constitutive production of TNF-α 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-α 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-α 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-α was achieved. Tumors derived from TNF-α 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-α knockdown tumors. Furthermore, culture supernatants from such cells failed to stimulate endothelial cell growth in vitro. We conclude that autocrine production of TNF-α 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. [Cancer Res 2007;67(2):585–92]
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Cited by
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Self-citationChronic inflammation and cytokines in the tumor microenvironment
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Mechanisms of Cisplatin Nephrotoxicity
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Metadata
- Authors
- Kulbe, H., Thompson, R., Wilson, J. L., Robinson, S., Hagemann, T., Fatah, R., Gould, D., Ayhan, A., & Balkwill, F.
- Venue
- Cancer Research
- Published
- 2007-01-15
- Volume
- 67
- Issue
- 2
- Pages
- 585-592
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W2144737008
- Cited by
- 386
- References
- 29
- FWCI
- 23.69
- Type
- journal article
- Language
- en
- Open access
- green
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- Kulbe, H., Thompson, R., Wilson, J. L., Robinson, S., Hagemann, T., Fatah, R., Gould, D., Ayhan, A., & Balkwill, F. (2007). The Inflammatory Cytokine Tumor Necrosis Factor-α Generates an Autocrine Tumor-Promoting Network in Epithelial Ovarian Cancer Cells. Cancer Research. https://doi.org/10.1158/0008-5472.can-06-2941
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