Limits...
The coxsackievirus and adenovirus receptor acts as a tumour suppressor in malignant glioma cells.

Kim M, Sumerel LA, Belousova N, Lyons GR, Carey DE, Krasnykh V, Douglas JT - Br. J. Cancer (2003)

Bottom Line: The coxsackievirus and adenovirus receptor has been shown to exhibit tumour suppression activity in human bladder and prostate cancer cells.In the current paper, we demonstrate that CAR is a tumour suppressor in glioma cells and that the extracellular D2 domain is not required for this inhibitory effect.This suggests that strategies to redirect adenoviruses to achieve CAR-independent infection will be necessary to realise the full potential of adenoviral vectors for cancer gene therapy.

View Article: PubMed Central - PubMed

Affiliation: Division of Human Gene Therapy, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.

ABSTRACT
The coxsackievirus and adenovirus receptor (CAR) is a membrane glycoprotein with a cytoplasmic domain, a transmembrane domain and an extracellular region consisting of two immunoglobulin-like domains, an amino-terminal immunoglobulin variable (IgV)-related domain (D1), which is distal to the cell surface, and a proximal IgC2 domain (D2). The coxsackievirus and adenovirus receptor has been shown to exhibit tumour suppression activity in human bladder and prostate cancer cells. In the current paper, we demonstrate that CAR is a tumour suppressor in glioma cells and that the extracellular D2 domain is not required for this inhibitory effect. This finding provides a biological basis for the observation that expression of CAR is downregulated in malignant glioma cells. This suggests that strategies to redirect adenoviruses to achieve CAR-independent infection will be necessary to realise the full potential of adenoviral vectors for cancer gene therapy.

Show MeSH

Related in: MedlinePlus

Schematic diagram of hCAR and deletion mutants. The coxsackievirus and adenovirus receptor comprises an extracellular region, a transmembrane domain (hatched rectangle) and a cytoplasmic domain (open rectangle). The extracellular region of wild-type CAR comprises an amino-terminal IgV-related domain designated D1 (solid oval), which is distal to the cell surface, and a proximal IgC2 domain designated D2 (open oval). The hCAR-tailless mutant is truncated after amino acid 260. The hCAR-GPI mutant consists of the extracellular domain of hCAR (corresponding to amino-acid residues 1–235) fused to the 37 carboxy-terminal amino acids of human DAF. The hCARΔD1 mutant lacks amino acids 21–144, while the hCARΔD2 mutant lacks amino acids 145–233 (Freimuth et al, 1999).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2741053&req=5

fig1: Schematic diagram of hCAR and deletion mutants. The coxsackievirus and adenovirus receptor comprises an extracellular region, a transmembrane domain (hatched rectangle) and a cytoplasmic domain (open rectangle). The extracellular region of wild-type CAR comprises an amino-terminal IgV-related domain designated D1 (solid oval), which is distal to the cell surface, and a proximal IgC2 domain designated D2 (open oval). The hCAR-tailless mutant is truncated after amino acid 260. The hCAR-GPI mutant consists of the extracellular domain of hCAR (corresponding to amino-acid residues 1–235) fused to the 37 carboxy-terminal amino acids of human DAF. The hCARΔD1 mutant lacks amino acids 21–144, while the hCARΔD2 mutant lacks amino acids 145–233 (Freimuth et al, 1999).

Mentions: We first constructed two previously described truncation mutant forms of hCAR–tailless hCAR, containing the extracellular domain, transmembrane domain and the first two amino acids from the cytoplasmic domain of hCAR, and glycosylphosphatidyl (GPI)-anchored hCAR, lacking both the transmembrane and cytoplasmic domains (Figure 1Figure 1


The coxsackievirus and adenovirus receptor acts as a tumour suppressor in malignant glioma cells.

Kim M, Sumerel LA, Belousova N, Lyons GR, Carey DE, Krasnykh V, Douglas JT - Br. J. Cancer (2003)

Schematic diagram of hCAR and deletion mutants. The coxsackievirus and adenovirus receptor comprises an extracellular region, a transmembrane domain (hatched rectangle) and a cytoplasmic domain (open rectangle). The extracellular region of wild-type CAR comprises an amino-terminal IgV-related domain designated D1 (solid oval), which is distal to the cell surface, and a proximal IgC2 domain designated D2 (open oval). The hCAR-tailless mutant is truncated after amino acid 260. The hCAR-GPI mutant consists of the extracellular domain of hCAR (corresponding to amino-acid residues 1–235) fused to the 37 carboxy-terminal amino acids of human DAF. The hCARΔD1 mutant lacks amino acids 21–144, while the hCARΔD2 mutant lacks amino acids 145–233 (Freimuth et al, 1999).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2741053&req=5

fig1: Schematic diagram of hCAR and deletion mutants. The coxsackievirus and adenovirus receptor comprises an extracellular region, a transmembrane domain (hatched rectangle) and a cytoplasmic domain (open rectangle). The extracellular region of wild-type CAR comprises an amino-terminal IgV-related domain designated D1 (solid oval), which is distal to the cell surface, and a proximal IgC2 domain designated D2 (open oval). The hCAR-tailless mutant is truncated after amino acid 260. The hCAR-GPI mutant consists of the extracellular domain of hCAR (corresponding to amino-acid residues 1–235) fused to the 37 carboxy-terminal amino acids of human DAF. The hCARΔD1 mutant lacks amino acids 21–144, while the hCARΔD2 mutant lacks amino acids 145–233 (Freimuth et al, 1999).
Mentions: We first constructed two previously described truncation mutant forms of hCAR–tailless hCAR, containing the extracellular domain, transmembrane domain and the first two amino acids from the cytoplasmic domain of hCAR, and glycosylphosphatidyl (GPI)-anchored hCAR, lacking both the transmembrane and cytoplasmic domains (Figure 1Figure 1

Bottom Line: The coxsackievirus and adenovirus receptor has been shown to exhibit tumour suppression activity in human bladder and prostate cancer cells.In the current paper, we demonstrate that CAR is a tumour suppressor in glioma cells and that the extracellular D2 domain is not required for this inhibitory effect.This suggests that strategies to redirect adenoviruses to achieve CAR-independent infection will be necessary to realise the full potential of adenoviral vectors for cancer gene therapy.

View Article: PubMed Central - PubMed

Affiliation: Division of Human Gene Therapy, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.

ABSTRACT
The coxsackievirus and adenovirus receptor (CAR) is a membrane glycoprotein with a cytoplasmic domain, a transmembrane domain and an extracellular region consisting of two immunoglobulin-like domains, an amino-terminal immunoglobulin variable (IgV)-related domain (D1), which is distal to the cell surface, and a proximal IgC2 domain (D2). The coxsackievirus and adenovirus receptor has been shown to exhibit tumour suppression activity in human bladder and prostate cancer cells. In the current paper, we demonstrate that CAR is a tumour suppressor in glioma cells and that the extracellular D2 domain is not required for this inhibitory effect. This finding provides a biological basis for the observation that expression of CAR is downregulated in malignant glioma cells. This suggests that strategies to redirect adenoviruses to achieve CAR-independent infection will be necessary to realise the full potential of adenoviral vectors for cancer gene therapy.

Show MeSH
Related in: MedlinePlus