|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
1
|
|
pubmed:dateCreated |
2004-1-21
|
|
pubmed:abstractText |
Overexpression of inhibitors of apoptosis (IAP) is one potential mechanism for tumor cells to evade immune surveillance. To determine whether immune-mediated killing of tumor cells can be enhanced by neutralization of IAP proteins, 2 novel eGFP-Smac fusion proteins (pro-Smac) were introduced into the poorly immunogenic mouse melanoma cell line, B16BL6-D5 (D5). Each fusion protein contained Smac and a cleavage site specific for granzyme B (GrB) or caspase 8, thereby targeting the 2 major killing mechanisms of cytotoxic T-lymphocyte (CTL) and NK cells. Expression of a pro-Smac fusion protein by D5 tumor cells greatly enhanced the susceptibility to killing by lymphokine-activated killer (LAK) cells or purified GrB. GrB-mediated killing was increased to a much greater extent when tumor cells expressed the eGFP-Smac fusion protein with a GrB cleavage site compared to a caspase 8 cleavage site. In contrast, perforin-deficient LAK cells, which lack GrB-mediated cytotoxicity but process normal ligands for death receptors, killed D5 tumor cells expressed pro-Smac with caspase 8 cleavage site more efficiently. Enhanced killing by GrB was also accompanied by processing of the fusion protein and increased caspase-3-like activity. These results indicate that killing of tumor cells can be amplified by targeting cell-mediated cytotoxic mechanisms via expression of pro-Smac fusion proteins.
|
|
pubmed:grant |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CASP3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CASP8 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Casp3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Casp8 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 8,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/DIABLO protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Diablo protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Green Fluorescent Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Luminescent Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Mitochondrial Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Mar
|
|
pubmed:issn |
0020-7136
|
|
pubmed:author |
|
|
pubmed:copyrightInfo |
Copyright 2003 Wiley-Liss, Inc.
|
|
pubmed:issnType |
Print
|
|
pubmed:volume |
109
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
85-94
|
|
pubmed:dateRevised |
2007-11-14
|
|
pubmed:meshHeading |
pubmed-meshheading:14735472-Animals,
pubmed-meshheading:14735472-Blotting, Western,
pubmed-meshheading:14735472-Carrier Proteins,
pubmed-meshheading:14735472-Caspase 3,
pubmed-meshheading:14735472-Caspase 8,
pubmed-meshheading:14735472-Caspases,
pubmed-meshheading:14735472-Cell Line, Tumor,
pubmed-meshheading:14735472-Flow Cytometry,
pubmed-meshheading:14735472-Green Fluorescent Proteins,
pubmed-meshheading:14735472-Humans,
pubmed-meshheading:14735472-Immunotherapy,
pubmed-meshheading:14735472-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:14735472-Killer Cells, Natural,
pubmed-meshheading:14735472-Luminescent Proteins,
pubmed-meshheading:14735472-Lymphocytes,
pubmed-meshheading:14735472-Mice,
pubmed-meshheading:14735472-Microscopy, Fluorescence,
pubmed-meshheading:14735472-Mitochondrial Proteins,
pubmed-meshheading:14735472-Neoplasms,
pubmed-meshheading:14735472-Plasmids,
pubmed-meshheading:14735472-Recombinant Fusion Proteins,
pubmed-meshheading:14735472-Retroviridae,
pubmed-meshheading:14735472-Subcellular Fractions
|
|
pubmed:year |
2004
|
|
pubmed:articleTitle |
Targeting and amplification of immune killing of tumor cells by pro-Smac.
|
|
pubmed:affiliation |
Laboratory of Cancer Immunobiology, Earle A Chiles Research Institute, Providence Portland Medical Center, Portland, OR 97213, USA.
|
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|
