686. CAR-Expression Is Essential for Tumor Inititation in Lung Cancer Xenografts
In: Molecular Therapy, Jg. 9 (2004-05-01), S. S260
Online
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Zugriff:
Top of pageAbstract Rationale: CAR, the Coxsackievirus Adenovirus Receptor, has primarily been studied in its role as the initial cell surface attachment receptor for Coxsackie and group C-Adenoviruses (Ad). Recent studies indicate that CAR serves to mediate homotypic cell-cell adhesion as a component of the tight junction and/or adherens junction. CAR's role in tumorigenesis has been considered, but no mechanistic studies probing this role have been reported. Experimental Design: Non-small cell lung cancer (NSCLC) cells with exuberant CAR expression (FACS: 99.9% positive w/ MCF 55.2) were stably transfected with control and AS-CAR vectors, and CAR(−)clones isolated (FACS: 1.9% positive w/ MCF 9.6). Cells were phenotypically characterized and tumorigenesis was compared in xenograft models. In separate experiments, CAR was functionally blocked using a monoclonal antibody and a specific ligand (Ad fiber knob), and the impact on tumor formation assessed. Results: Expectedly, CAR (−) cells were refractory to Ad-transduction and demonstrated marked reductions in CAR-mRNA by RT-PCR. Silencing CAR expression in cells that exhibited relatively “high” surface expression of this molecule profoundly inhibited their ability to develop xenografts in host mice (Day 40 tumor volume: CAR (+) cells 574 + 304 mm3, CAR (−) cells 0 mm3; n = 10 scid/scid mice, p
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686. CAR-Expression Is Essential for Tumor Inititation in Lung Cancer Xenografts
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Autor/in / Beteiligte Person: | Zhang, Ling ; Batra, Raj K. ; Escuadro, Brian ; Sharma, Sherven ; Qin, Min |
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Zeitschrift: | Molecular Therapy, Jg. 9 (2004-05-01), S. S260 |
Veröffentlichung: | Elsevier BV, 2004 |
Medientyp: | unknown |
ISSN: | 1525-0016 (print) |
DOI: | 10.1016/j.ymthe.2004.06.583 |
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