Interestingly, the primary tumor C15 showed a profile of TNF-sensitive tumor while C17, C18 and C19 which were derived from metastasis have a typical profile of TNF-resistant cells.
In contrast, a mutein of TNF-alpha, designated as F4236, having the cell-adhesive sequence (Tyr-Ile-Gly-Ser-Arg) at the N-terminus of the TNF molecule did not enhance metastasis, but rather exhibited similar antitumor activity to wild-type TNF-alpha in fibrosarcoma-bearing mice.
We have related these data to expression of some of the controlling elements of the enzymes, namely tissue inhibitors of metastasis (TIMPs) and tumor necrosis factor (TNF). mRNA for MMP-2 was found in the majority of cases and localized to stromal areas with maximal expression adjacent to neoplastic areas.
In one case it has been shown that a TNF gene-transfected tumour showed no tumour growth inhibition in vivo but that TNF augmented metastasis of these cells.
In HNSCC, enhanced expression of TNF receptors on the cancer cells occurs and is likely to contribute to the regulation of TNF and its activation of tumor cells within the tumor microenvironment; targeting these receptors in cancer cells may provide a new approach to controlling tumor growth and metastasis.
In this study, to explore the possibility that the mutations of death receptors are involved in the metastasis mechanism, we analyzed the death domains of Fas and tumor necrosis factor-related apoptosis-inducing ligand-receptor 1 and -2 (TRAIL-R1 and -R2) genes for the detection of somatic mutations in 57 breast cancers with (n = 34) or without (n = 23) metastasis to the regional lymph nodes.
Several cytokines including members of the transforming growth factor-beta (TGF-beta) and tumor necrosis factor (TNF) families have been implicated in the homing mechanism of breast cancer metastasis.
Activation of the transcription factor nuclear factor kappaB (NF-kappaB), a TNF-alpha downstream signaling component, is associated with several human illnesses, including cancer, and NF-kappaB controls the expression of multiple genes involved in tumor progression and metastasis.
We set out to examine the role of MnSOD in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis, thought to be a first-line tumor surveillance mechanism and failure to undergo apoptosis might contribute to metastasis formation.
We studied how the level of vascular cell adhesion molecule-1 (VCAM-1), one of the key molecules in the development of atherosclerosis as well as carcinogenesis and metastasis, might be affected by bisacurone in tumor necrosis factor-alpha (TNF-alpha)-activated human umbilical vein endothelial cells (HUVECs).
Furthermore, deregulated TNF expression within the tumor microenvironment appears to favor malignant cell tissue invasion, migration and ultimately metastasis formation.
Tumor necrosis factor alpha (TNFalpha) is a major proinflammatory cytokine that plays crucial roles in tumor progression, including tumor invasion and metastasis in the tumor microenvironment.
The tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a potent inducer of tumor cell apoptosis, but concerns of considerable liver toxicity limit its uses in human cancer therapy.Here, we show that i.v. injected Escherichia coli DH5alpha (E. coli DH5alpha) specifically replicates in solid tumors and metastases in live animals.
These findings support a model in which treatment of tumors with Ad.Egr-TNF and IR is mediated by local and distant immune-mediated antitumor effects that suppress the development of metastases.
TNF-α expression by tumor cells may be an efficient immunological escape mechanism by inflammation-enhanced metastases and probably by induction of apoptosis in tumor-infiltrating CD8+ immune cells resulting in a down regulation of the tumoral immune response.
Independent and cooperative roles of tumor necrosis factor-alpha, nuclear factor-kappaB, and bone morphogenetic protein-2 in regulation of metastasis and osteomimicry of prostate cancer cells and differentiation and mineralization of MC3T3-E1 osteoblast-like cells.
For instance, prostate cancer metastasis is associated with the infiltration of lymphocytes into advanced tumours and the upregulation of two tumour-necrosis-factor family members: receptor activator of nuclear factor-κB (RANK) ligand (RANKL) and lymphotoxin.
To examine how TNFα modulates the progression and metastasis of nasopharyngeal carcinoma, we used Affymetrix chips to identify TNFα-inducible genes that are dysregulated in this tumor.