TRAIL promotes the survival, migration and proliferation of vascular smooth muscle cells

Secchiero, Paola; Zerbinati, Carlotta; Rimondi, Erika; Corallini, Federica; Milani, Daniela; Grill, Vittorio; Forti, Giorgio; Capitani, Silvano; Zauli, Giorgio

doi:10.1007/s00018-004-4197-6

Cited by 127 publications

(130 citation statements)

References 20 publications

Supporting

Mentioning

127

Contrasting

Order By: Relevance

“…TRAIL has been shown to lead to increased proliferation in some cell types, an effect which is abrogated by pharmacological inhibitors of the Erk pathway (Secchiero et al, 2004). We therefore tested whether TRAIL could trigger proliferative instead of apoptotic signalling in SW620 cells.…”

Section: Trail-resistance In Sw620 Cells Is Downstream Of Bid Cleavagementioning

confidence: 99%

A mitochondrial block and expression of XIAP lead to resistance to TRAIL-induced apoptosis during progression to metastasis of a colon carcinoma

et al. 2008

View full text Add to dashboard Cite

A pair of isogenic colon carcinoma cells, SW480 and 620, was used to investigate the mechanisms of acquired tumour necrosis factor-related apoptosis-inducing ligand (TRAIL)-resistance during tumour progression. Whereas primary tumour SW480 cells are sensitive to TRAILinduced apoptosis, metastatic SW620 cells are resistant. The apoptotic signalling activated by TRAIL in SW480 cells is a type II pathway. We show that in SW620 cells, although caspase-8 is recruited and activated at the deathinducing-signalling complex and Bid is cleaved, this does not lead to caspase-9 activation. Comparison of Bcl-2, Bcl-xL and Mcl-1 levels in both cell lines showed no difference. In SW620 cells transfected with a tBid-GFP construct, tBid-GFP was correctly localized to the mitochondria. Thus, the resistance of SW620 cells is at the level of the mitochondria that can withstand large amounts of tBid. Although caspase-3 was directly cleaved by caspase-8 in SW620 cells to yield the p20 fragment, no further autocatalytic maturation into the p17 fragment was observed. We show that, in contrast to SW480 cells, the SW620 cell line expresses high amounts of X-linked inhibitor of apoptosis (XIAP). Downregulation of XIAP with bortezomib or small-interfering RNA was sufficient to restore the sensitivity of SW620 cells to TRAILinduced apoptosis in the absence of SMAC/Diablo or cytochrome c release from the mitochondria. Thus, SW620 cells have developed a dual resistance to TRAIL-induced apoptosis: a block at the level of the mitochondria and, after a conversion to a type I pathway, an increased expression of XIAP which inhibits this pathway.

show abstract

Section: Trail-resistance In Sw620 Cells Is Downstream Of Bid Cleavagementioning

confidence: 99%

A mitochondrial block and expression of XIAP lead to resistance to TRAIL-induced apoptosis during progression to metastasis of a colon carcinoma

et al. 2008

View full text Add to dashboard Cite

show abstract

“…In normal cells that are generally resistant to the apoptotic effects, TRAIL induces proliferation of vascular smooth muscle cells, synovial fibroblasts and T lymphocytes [9][10][11]. Similarly, TRAIL treatment stimulated proliferation of apoptosis-resistant malignant cells, such as leukemia, neuroblastoma, renal cell carcinoma, and colon carcinoma cell lines [8,12,13].…”

Section: Introductionmentioning

confidence: 99%

Multiple effects of TRAIL in human carcinoma cells: Induction of apoptosis, senescence, proliferation, and cytokine production

Levina

Marrangoni

DeMarco

et al. 2008

Experimental Cell Research

View full text Add to dashboard Cite

TRAIL is a death ligand that induces apoptosis in malignant but not normal cells. Recently the ability of TRAIL to induce proliferation in apoptosis-resistant normal and malignant cells was reported. In this study, we analyzed TRAIL effects in apoptosis sensitive MCF7, OVCAR3 and H460 human tumor cell lines. TRAIL at low concentrations preferentially induced cell proliferation. At 100 ng/ ml apoptotic death was readily observed, however surviving cells acquired higher proliferative capacity. TRAIL stimulated production of several cytokines, IL-8, RANTES, MCP-1 and bFGF, and activation of caspases 1 and 8 was essential for this effect. Antibodies to IL-8, RANTES, and bFGF blocked TRAIL-induced cell proliferation and further stimulated apoptosis. For the first time, we report that high TRAIL concentrations induced cell senescence as determined by altered morphology and expression of several senescence markers: SA-β-gal, p21 Waf1/Cip1 , p16 INK4a , and HMGA. Caspase 9 inhibition protected TRAIL-treated cells from senescence, whereas inhibition of caspases 1 and 8 increased yield of SLP cells. In conclusion, in cultured human carcinoma cells, TRAIL therapy results in three functional outcomes, apoptosis, proliferation and senescence. TRAIL induced proapoptotic and prosurvival responses correlate with strength of signaling. TRAIL-induced cytokine production is responsible for its proliferative and prosurvival effects.

show abstract

“…This phenomenon has been described for several other members of the TNF family and it is thought that one pathway potentially pre-dominates, but that a build-up of intracellular regulators can flick the switch from cell death to proliferation and vice versa. 2,3 For example, TRAIL has been shown to promote cell survival and proliferation of endothelial and vascular smooth muscle cells 4,5 and to regulate erythroid and monocytic maturation. 6 Evidence is accumulating that TRAIL has multiple effects also on tumor cells.…”

mentioning

confidence: 99%

The pleiotropic effect of TRAIL on tumor-like synovial fibroblasts from rheumatoid arthritis patients is mediated by caspases

et al. 2009

View full text Add to dashboard Cite

The tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) has gained much attention as a possible therapeutic reagent for the treatment of tumors, as TRAIL was originally described to induce apoptosis specifically in cancer cells, but not in normal cells. Fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA) patients exhibit tumor-like features and we have described earlier that TRAIL induces apoptosis only in a subset of RA FLS, but an induction of proliferation in the surviving cells. This observation corresponds to the pleiotropic effects of TRAIL observed on primary human tumor cells. Here, we describe that the PI3 kinase/Akt-signaling pathway, but not that of the MAP kinases ERK and p38, protects RA FLS from TRAIL-induced apoptosis by modulating the expression of the cell survival regulators p21, XIAP, Mcl-1 and RIP. Moreover, we found that not only TRAIL-induced apoptosis, but also TRAIL-triggered proliferation in RA FLS is mediated by caspases with a crucial role for caspase 8. TRAIL was found to induce degradation of p21 and p27 that was caspase-dependent, but independent of the ERK, p38 and PI3 kinase/Akt-signaling pathways. The finding that TRAIL-triggered proliferation and apoptosis share intracellular routes has to be taken in consideration in defining therapeutic strategies on the basis of the administration of TRAIL. In recent years, considerable attention has been focused on the potential benefits of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) in cancer therapy, as a broad range of cancer cells are sensitive to TRAIL-induced apoptosis (reviewed in 1 ). In addition, the use of TRAIL in combination with chemotherapeutic agents or irradiation strengthens its apoptotic effects and frequently sensitizes the otherwise TRAIL-resistant tumor cells. It is important that TRAIL does not seem to be toxic to normal cells, as TRAIL exposure shows no toxic side effects of therapeutically relevant doses in primates.Tumor necrosis factor (TNF)-related apoptosis-inducing ligand can interact with five different receptors: four membrane-anchored receptors TRAIL-R1 (DR4), TRAIL-R2 (DR5), TRAIL-R3 (DcR1) and TRAIL-R4 (DcR2) and a soluble decoy receptor osteoprotegerin. The receptors TRAIL-R1 and -R2 contain an intracellular cytoplasmic sequence motif, known as the death domain (DD), and can induce apoptosis through activation of caspases (reviewed in 2 ). Nevertheless, TRAIL-receptors R1 and R2 not only trigger apoptosis, but also proliferation and differentiation depending on the cell type (reviewed in 2 ). This phenomenon has been described for several other members of the TNF family and it is thought that one pathway potentially pre-dominates, but that a build-up of intracellular regulators can flick the switch from cell death to proliferation and vice versa. 2,3 For example, TRAIL has been shown to promote cell survival and proliferation of endothelial and vascular smooth muscle cells 4,5 and to regulate erythroid and monocytic maturation. 6 Evidence is accumulati...

show abstract

TRAIL promotes the survival, migration and proliferation of vascular smooth muscle cells

Cited by 127 publications

References 20 publications

A mitochondrial block and expression of XIAP lead to resistance to TRAIL-induced apoptosis during progression to metastasis of a colon carcinoma

A mitochondrial block and expression of XIAP lead to resistance to TRAIL-induced apoptosis during progression to metastasis of a colon carcinoma

Multiple effects of TRAIL in human carcinoma cells: Induction of apoptosis, senescence, proliferation, and cytokine production

The pleiotropic effect of TRAIL on tumor-like synovial fibroblasts from rheumatoid arthritis patients is mediated by caspases

Contact Info

Product

Resources

About