TRAIL-induced eradication of primary tumour cells from multiple myeloma patient bone marrows is not related to TRAIL receptor expression or prior chemotherapy

Apo2L/TRAIL and its death and decoy receptors

“…6,15 Surveys of cancer cell lines and tumours did not reveal correlations between DcR expression and Apo2L/TRAIL resistance, but almost all of these studies relied on detecting mRNA 54,57,58 rather than looking for cell surface expression of the proteins. 59 It is possible that even detection of receptors by Western blot 45 may be misleading as the DcRs sometimes localise within the cell rather than at the cell surface. 60,61 It is not fully understood how widespread surface expression of the decoy receptors is in tumour or normal cells, or precisely how these receptors modulate Apo2L/TRAIL signalling.…”

“…Indeed, Apo2L/TRAIL is effective at inducing apoptosis in most multiple myeloma patient samples regardless of their resistance or sensitivity to chemotherapeutic drugs, 86 or prior exposure to chemotherapy. 59 In mouse models, Apo2L/ TRAIL demonstrated remarkable efficacy against tumour xenografts of colon carcinoma, 87,88 breast carcinoma 4 , multiple myeloma, 86 or glioma 89,90 cell lines. Moreover, combinations of Apo2L/TRAIL and certain DNA-damaging drugs 3,91 or radiotherapy 92 exerted synergistic antitumour xenograft activity.…”

Modulation of tumor necrosis factor related apoptosis-inducing ligand (TRAIL) receptors in a human osteoclast model in vitro

“…While malignant plasma cells express TRAIL receptors, there appears to be no relation between TRAIL sensitivity and its pattern of receptor expression (Lincz et al, 2001). While apoptosis was induced in vitro, the same profile is not observed in vivo in MM patients.…”

Intra-articular adenoviral-mediated gene transfer of trail induces apoptosis of arthritic rabbit synovium

“…16 TRAIL induces apoptosis by binding to and cross-linking death-domain containing receptors, TRAIL-R1 (DR4) and TRAIL-R2 (DR5). 14,[17][18][19][20][21] In addition to these active receptors, several decoy receptors for TRAIL that lack active death domains have been identified (TRAIL-R3, TRAIL-R4 and OPG). 19,[22][23][24][25][26] While it has been postulated that these decoy receptors may play a role in the regulation of TRAIL mediated apoptosis no correlation between TRAIL susceptibility and the expression of decoy receptors was found in a screen of primary human melanoma and myeloma cell lines.…”

“…19,[22][23][24][25][26] While it has been postulated that these decoy receptors may play a role in the regulation of TRAIL mediated apoptosis no correlation between TRAIL susceptibility and the expression of decoy receptors was found in a screen of primary human melanoma and myeloma cell lines. 17,27 The intriguing aspect to TRAIL-induced apoptosis is that TRAIL has a potent cytotoxic effect on a number of human tumor cells, but generally has no effect on the viability of normal cells. 13,14 The ability of TRAIL to selectively induce apoptosis in transformed cells makes it more attractive as an apoptosis-inducing agent than other pro-apoptotic proteins such as FasL and TNFa that, in addition to their strong anti-tumor effects, have severe toxic side effects.…”