The Use of TNF Family Ligands and Receptors and Agents which Modify their Interaction as Therapeutic Agents

Gardnerova, M.; Blanqué, R.; Gardner, Carol R.

doi:10.2174/1389450003349092

Cited by 16 publications

(9 citation statements)

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“…CD95 ligand (CD95L/FasL), a member of the death ligand family, which also includes TNFα and TRAIL has been viewed as an apoptosis‐inducing ligand and members of this family are therefore being considered as potential antitumor reagents (Gardnerova et al , 2000). CD95L is expressed either on cell membranes (mCD95L) or in soluble form (sCD95L) and induces apoptosis when it triggers its cognate receptor CD95 (APO‐1/Fas) (Peter et al , 2003).…”

Section: Introductionmentioning

confidence: 99%

CD95 ligand induces motility and invasiveness of apoptosis-resistant tumor cells

Barnhart

Legembre

Pietras

et al. 2004

EMBO J

272

296

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The apoptosis-inducing death receptor CD95 (APO-1/Fas) controls the homeostasis of many tissues. Despite its apoptotic potential, most human tumors are refractory to the cytotoxic effects of CD95 ligand. We now show that CD95 stimulation of multiple apoptosis-resistant tumor cells by CD95 ligand induces increased motility and invasiveness, a response much less efficiently triggered by TNFa or TRAIL. Three signaling pathways resulting in activation of NF-jB, Erk1/2 and caspase-8 were found to be important to this novel activity of CD95. Gene chip analyses of a CD95-stimulated tumor cell line identified a number of potential survival genes and genes that are known to regulate increased motility and invasiveness of tumor cells to be induced. Among these genes, urokinase plasminogen activator was found to be required for the CD95 ligand-induced motility and invasiveness. Our data suggest that CD95L, which is found elevated in many human cancer patients, has tumorigenic activities on human cancer cells. This could become highly relevant during chemotherapy, which can cause upregulation of CD95 ligand by both tumor and nontumor cells.

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Section: Introductionmentioning

confidence: 99%

CD95 ligand induces motility and invasiveness of apoptosis-resistant tumor cells

Barnhart

Legembre

Pietras

et al. 2004

EMBO J

272

296

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“…The actions of RANKL are controlled in vivo by an endogenous TNF superfamily decoy receptor called osteoprotegerin (Gardnerova et al, 2000;Lacey et al, 2000). Osteoclast development in vivo is also under the separate control of calcitonin which inhibits cell motility and actin ring formation and bone resorptive mechanisms Marzia et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

“…The fusion and differentiation of osteoclasts is a complex process which is influenced by several cytokines and growth factors (Reddy, 2004;Takayanagi, 2005;Fuller et al, 2006). The actions of RANKL are controlled in vivo by an endogenous TNF superfamily decoy receptor called osteoprotegerin (Gardnerova et al, 2000;Lacey et al, 2000). Osteoclast development in vivo is also under the separate control of calcitonin which inhibits cell motility and actin ring formation and bone resorptive mechanisms Marzia et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Morphological analysis of osteoclastogenesis induced by RANKL in mouse bone marrow cell cultures

Gardner¹

2007

Cell Biology International

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Under the influence of RANKL, in the presence of M-CSF, monocyte/macrophage precursor cells entered the osteoclast lineage and expressed the osteoclast marker tartrate-resistant acid phosphatase (TRAP). These cells were motile and began to differentiate by contacting and fusing together, initially forming cells with several nuclei. All sizes of cells continued to fuse, forming larger cells with more than 6 and as many as 50 nuclei. The degree of osteoclastogenesis was related to the concentration of RANKL. High cell density changed osteoclast morphology from a more rounded form with cytoplasm extended all round the cell to a form with cytoplasm concentrated around the nuclei and more restricted multiple cytoplasmic extensions. At optimal cell density and RANKL concentrations the large numbers of rounded cells fused into large cytoplasmic masses. On reaching a critical size, osteoclasts assumed a spread morphology with a peripheral ring structure. Most of the nuclei were associated with the peripheral ring. When cytoplasmic masses were present, rings also formed within the mass, often with no contact with the cell periphery. All forms of RANKL-induced osteoclastogenesis were blocked by the endogenous decoy receptor osteoprotegerin and were also strongly reduced by calcitonin, with the later arriving morphological categories being the first to disappear.

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“…TNF-α is a pleiotropic cytokine exerting multifunction, mainly in inflammation and immune responses [4,5] . It is able to exert an antitumor activity, because of its direct cytotoxicity on tumor cells and the induction of hemorrhagic necrosis in tumors.…”

Section: Discussionmentioning

confidence: 99%

Time-and dose-dependent up-regulation of TNF-α mRNA after irradiation of human NSCLC cell lines in vitro

Liu

2006

Chin. J. Cancer Res.

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Objective: Even though radiotherapy plays a major role in the local treatment of non-small cell lung cancer (NSCLC), little is known about the molecular effects of irradiation in this tumor. In the present study, we examined two NSCLC cell lines for their endogenous production of TNF-α after irradiation. To investigate the radiation-induced TNF-α production in NSCLC cell lines. Methods: Two human NSCLC cell lines (A549: squamous; NCI-H596: adenosquamous) were investigated for their TNF-α mRNA (real-time RT-PCR) after exposure to different irradiation doses (2, 5, 10, 20, 30, 40 Gy) and time intervals (1, 3, 6, 12, 24, 48 or 72 h). The TNF-α mRNA expression was quantified by real-time RT-PCR. The clonogenic survival was evaluated after irradiation with 2, 4, 6 and 8 Gy. Results: Non-irradiated NSCLC cells exhibited no or very low TNF-α expression. For the NCI-H596 cell line, TNF-α expression was significantly elevated 1∼12 h (maximum 6h: 568fold increase relative to unirradiated cells) in a time-dependent manner. The radiation-induced increase could be observed after irradiation with 2 Gy reaching maximal at 40 Gy, with 83 times higher than normal controls. The clonogenic survival of these cell lines was nearly identical. Conclusion: NCI-H596 cells produce significant quantities of TNF-α following irradiation in a time-and dose-dependent manner. The pro-inflammatory cytokine TNF-α is a key mediator for the pathogenesis of radiation pneumonitis. Radiation-induced endogenous TNF-α expression in NSCLC cells may affect the normal lung adjacent to the tumor and may be associated with an adverse clinical outcome of the patient.

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The Use of TNF Family Ligands and Receptors and Agents which Modify their Interaction as Therapeutic Agents

Cited by 16 publications

References 0 publications

CD95 ligand induces motility and invasiveness of apoptosis-resistant tumor cells

CD95 ligand induces motility and invasiveness of apoptosis-resistant tumor cells

Morphological analysis of osteoclastogenesis induced by RANKL in mouse bone marrow cell cultures

Time-and dose-dependent up-regulation of TNF-α mRNA after irradiation of human NSCLC cell lines in vitro

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