The Inflammatory Cytokine Tumor Necrosis Factor-α Generates an Autocrine Tumor-Promoting Network in Epithelial Ovarian Cancer Cells

Abstract

Constitutive expression of the inflammatory cytokine tumor

Tumor necrosis factor deficiency inhibits mammary tumorigenesis and a tumor necrosis factor neutralizing antibody decreases mammary tumor growth in neu/erbB2 transgenic mice

“…Although it is clear in the current study that TNF can stimulate the proliferation of the preneoplastic neu-erbB2-overexpressing mammary epithelium, neither the number of neu/erbB2-driven hyperplasias nor the proliferative rate of the tumors per se were different between the TNF+/+ and TNF−/− mice. A possible explanation for this observation is that TNF may stimulate vasculogenesis, as shown by Kulbe et al (36) and Li et al (41) in other models, thus providing the hyperplasias and tumors with an environment more favorable for expansion. Furthermore, in the absence of TNF, or in the presence of the TNF-neutralizing antibody, the vasculature may lose this positive stimulus, and thus, tumor growth is slowed, as we show here.…”

“…In addition to its stimulatory role in skin carcinogenesis models, TNF promotes the growth of ovarian cancer. Unlike normal ovarian epithelium, ovarian tumor cells secrete TNF (35), which acts in an autocrine or paracrine manner by stimulating an increased release of chemokines, cytokines, and vascular endothelial growth factor, all potentially involved in tumor growth and neovascularization (36). Furthermore, ovarian tumors from TNF knockdown cells had reduced growth, metastasis, and vascularization in vivo, compared with TNF+/+ or mock-transfected cells (36).…”

“…Unlike normal ovarian epithelium, ovarian tumor cells secrete TNF (35), which acts in an autocrine or paracrine manner by stimulating an increased release of chemokines, cytokines, and vascular endothelial growth factor, all potentially involved in tumor growth and neovascularization (36). Furthermore, ovarian tumors from TNF knockdown cells had reduced growth, metastasis, and vascularization in vivo, compared with TNF+/+ or mock-transfected cells (36). Finally, hepatic carcinogenesis induced by a choline-deficient, ethionine-supplemented diet, as well as carcinogen-induced colorectal carcinogenesis, were found to be decreased in TNFR1 null mice (37,38).…”

Eryngium foetidum Suppresses Inflammatory Mediators Produced by Macrophages

“…TNF also involves in tumor angiogenesis, invasive, and metastasis. It enhances cytokines, chemokines, and angiogenic factor expression which promotesneovascularization to support tumor growth (Nabors et al, 2003;Kulbe et al, 2007). TNF increases the invasiveness of tumor cells by inducing expression of matrix metalloproteinase (MMP) (Esteve et al, 2002;Cheng et al, 2007).…”

Identification of TNF-α and MMP-9 as potential baseline predictive serum markers of sunitinib activity in patients with renal cell carcinoma using a human cytokine array

“…Pathological regulation of TNF-a has been related to primary and metastatic cancer promotion, directly or via a complex network of cytokines, chemokines, and matrix metalloproteases (Kulbe et al, 2007). TNF-a can be secreted by immune-related cells and tumour cells, and it has been suggested to act in an autocrine/ paracrine way to promote cancer development (Harrison et al, 2007).…”