Specific resistance upon lentiviral TRAIL transfer by intracellular retention of TRAIL receptors

Wenger, Till; Mattern, J; Penzel, Roland; Gaßler, Nikolaus; Haas, Tobias L.; Sprick, Martin R.; Walczak, Henning; Krammer, Peter H.; Debatin, Klaus‐Michael; Herr, Ingrid

doi:10.1038/sj.cdd.4401867

Cited by 21 publications

(14 citation statements)

References 55 publications

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“…LV production was performed as previously described. 25,26 Transduction of MSC Cells were seeded in six-well plates at 2 Â 10 5 -2 Â 10 6 cells per well in 2-5 ml MSC medium containing 8 mg ml À1 polybrene and virus was added to the cells at different multiplicities of infection. The plates were centrifuged at 1200 r.p.m., 37 1C for 1 h and incubated at 37 1C.…”

Section: Lentivirus Construction and Productionmentioning

confidence: 99%

Improved lentiviral transduction of human mesenchymal stem cells for therapeutic intervention in pancreatic cancer

et al. 2008

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Genetic modification of human bone marrow mesenchymal stem cells (MSC) is highly valuable for their exploitation in basic science and therapeutic applications, for example in cancer. We present here a new, fast and easy-to-use method to enrich a functional population of lentiviral (LV)-transduced MSC expressing enhanced green fluorescent protein (eGFP). We replaced the eGFP gene by a fusion gene of puromycin acetyltransferase and eGFP. Upon LV gene transfer and puromycin selection, we quickly obtained a pure transduced MSC population, in which growth, differentiation capacity and migration preferences were not compromised. Furthermore, we are the first to report the migration velocity of MSC among which 30% were moving and velocity of about 15 mm h À1 was not altered by LV transduction. Manipulated MSC underwent senescence one passage earlier than non-transduced cells, suggesting the use for therapeutic intervention in early passage numbers. Upon tail vein application in nude mice, the majority of LV-transduced MSC could be detected in human orthotopic pancreatic tumor xenografts and to a minor extent in mouse liver, kidney and lung. Together, LV transduction of genes to MSC followed by puromycin selection is a powerful tool for basic research and improves the therapeutic prospects of MSC as vehicles in gene therapy.

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Section: Lentivirus Construction and Productionmentioning

confidence: 99%

Improved lentiviral transduction of human mesenchymal stem cells for therapeutic intervention in pancreatic cancer

et al. 2008

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“…In this case, TRAILsensitive cells would be killed by the TRAIL application, whereas the remaining resistant tumor cells would survive and proliferate. 91 Hypoxic environments, which are often present in growing solid tumors, are known to induce the up-regulation of hypoxia-inducible factor-1␣. This transcription factor binds to hypoxia-response elements, thereby inducing many hypoxia-response genes, 92 such as VEGF.…”

Section: Influence Of the Tumor Microenvironment On Trail-induced Apomentioning

confidence: 99%

On the TRAIL to therapeutic intervention in liver disease

2007

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Hepatocellular carcinoma (HCC) ranks among the 10 most common cancers worldwide. The fact that HCC is resistant to conventional chemotherapy and is rarely amenable to radiotherapy leaves this disease with no effective therapeutic options and a very poor prognosis. Therefore, the development of more effective therapeutic tools and strategies is much needed. HCCs are phenotypically and genetically heterogeneous tumors that commonly emerge on a background of chronic liver diseases, most of which culminate in cirrhosis, such as alcoholic cirrhosis and chronic hepatitis B and C infections. This review outlines recent findings on the progression of liver disease, including our knowledge of the role of apoptotic processes, with an emphasis on the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). The proapoptotic and antiapoptotic properties of TRAIL, its involvement in liver injury, and its potential as a therapeutic agent in fibrosis and HCC are discussed. Several contradictory and confusing data have not yet been resolved or placed into perspective, such as the influence of factors that determine the TRAIL sensitivity of target cells, including the tumor microenvironment or cirrhotic tissue. Therefore, we assess these data from the perspectives of gastroenterologists (P.S. and M.W.B.) and a molecular oncologist (I.H.) with research interests in liver injury, apoptosis, and experimental therapeutics. (HEPATOLOGY

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“…Many cancer cells are primarily resistant to apoptosis, which is usually due to down-regulation of the apoptosis pathways and/or activation of cell survival signals through genetic and epigenetic aberrations acquired during transformation (1,2). In addition, cancer cells acquire apoptosis resistance during chemotherapy (secondary or acquired apoptosis resistance) (3)(4)(5). Acquired apoptosis resistance has been an increasing concern because it has emerged as an important mechanism underlying acquired chemoresistance (6,7).…”

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confidence: 99%

“…The molecular basis for acquired TRAIL resistance has not been well elucidated (4,5,18). We have recently established acquired TRAIL resistance in lung cancer cell lines by continuously exposing the TRAIL-sensitive lung cancer cells to nontoxic doses and gradually increasing the concentrations of TRAIL (19,20).…”

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confidence: 99%

Epidermal Growth Factor Receptor-mediated Tissue Transglutaminase Overexpression Couples Acquired Tumor Necrosis Factor-related Apoptosis-inducing Ligand Resistance and Migration through c-FLIP and MMP-9 Proteins in Lung Cancer Cells

Bai

et al. 2011

Journal of Biological Chemistry

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(MMP-9) was suppressed when TGM2 was inhibited, suggesting that TGM2 potentiates cell migration through up-regulating MMP-9 expression. We found that EGF receptor (EGFR) was highly active in the TRAIL-resistant cells, and suppression of EGFR dramatically reduced TGM2 expression. We further determined JNK and ERK, but not Akt and NF-B, are responsible for EGFR-mediated TGM2 expression. These results identify a novel pathway that involves EGFR, MAPK (JNK and ERK), and TGM2 for acquired TRAIL resistance and cell migration in lung cancer cells. Because TGM2 couples TRAIL resistance and cell migration, it could be a molecular target for circumventing acquired chemoresistance and metastasis in lung cancer.

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Specific resistance upon lentiviral TRAIL transfer by intracellular retention of TRAIL receptors

Cited by 21 publications

References 55 publications

Improved lentiviral transduction of human mesenchymal stem cells for therapeutic intervention in pancreatic cancer

Improved lentiviral transduction of human mesenchymal stem cells for therapeutic intervention in pancreatic cancer

On the TRAIL to therapeutic intervention in liver disease

Epidermal Growth Factor Receptor-mediated Tissue Transglutaminase Overexpression Couples Acquired Tumor Necrosis Factor-related Apoptosis-inducing Ligand Resistance and Migration through c-FLIP and MMP-9 Proteins in Lung Cancer Cells

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