Molecular and cellular insights into the coxsackie–adenovirus receptor: role in cellular interactions in the stem cell niche

Hauwel, Mathieu; Furon, Emeline; Gasque, Philippe

doi:10.1016/j.brainresrev.2004.12.017

Cited by 23 publications

(15 citation statements)

References 63 publications

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Section: Discussionmentioning

confidence: 99%

“…However, CAR is a multifaceted molecule expressed by many cell types and fulfilling many but yet poorly defined cellular functions (50). It behaves typically as an adhesion molecule promoting cell aggregation and may play role in embryogenesis and stem cell lineage (50). Overexpression of CAR in radiation-resistant cancer stem-like cell may be caused by preferential killing of cancer cells with low CAR expression by radiation or radiation-induced CAR expression.…”

Section: Discussionmentioning

confidence: 99%

“…To assess the efficacy of adenovirus replication in vivo, we removed whole tumors from mice 3 d after they were treated only once with various adenoviruses; the tumors were homogenized in 0.5 mL of cold PBS and centrifuged. The viral vector replication in the supernatant of tumor lysate was determined using the tissue culture infectious dose 50 (TCID 50 ) assay in fresh 293 cells as described previously (40).…”

Section: Methodsmentioning

confidence: 99%

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Treatment of Radioresistant Stem-Like Esophageal Cancer Cells by an Apoptotic Gene-Armed, Telomerase-Specific Oncolytic Adenovirus

Zhang

Komaki

Wang

et al. 2008

Clinical Cancer Research

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Purpose: Radioresistance may be caused by cancer stem cells (CSC). Because CSCs require telomerase to proliferate, a telomerase-specific oncolytic adenoviral vector carrying apoptotic tumor necrosis factor–related apoptosis-inducing ligand and E1A gene (Ad/TRAIL-E1) may preferentially target CSCs. Experimental Design: We established two pairs of parental and radioresistant (R) esophageal carcinoma cell lines (Seg-1, Seg-1R and TE-2, TE-2R) by fractionated irradiation. Stem cell markers were measured by Western blotting and flow cytometry. Serial sorting was used to enrich stem-like side population cells. Telomerase activity, transgene expression, antitumor activity, apoptosis induction, and viral replication were determined in vitro and/or in vivo. Results: Expression of the stem cell markers β-catenin, Oct3/4, and β1 integrin in Seg-1R cells was 29.4%, 27.5%, and 97.3%, respectively, compared with 4.8%, 14.9%, and 45.3% in Seg-1 cells (P < 0.05). SP levels in Seg-1R and TE-2R cells were 14.6% and 2.7%, respectively, compared with 3.4% and 0.3% in Seg-1 and TE-2 cells. Serial sorting of Seg-1R SP cells showed enrichment of the SP cells. Telomerase activities in Seg-1R, Seg-1R SP, and TE-2R cells were significantly higher than in Seg-1, Seg-1R non-SP, and TE-2 cells, respectively (P < 0.05). Seg-1R and TE-2R cells were more sensitive to Ad/TRAIL-E1 than parental cells. Increased Coxsackie-adenovirus receptor and elevated transgene expressions were found in the radioresistant cells. Ad/TRAIL-E1 resulted in significant tumor growth suppression and longer survival in Seg-1R–bearing mice (P < 0.05) with no significant toxicity. Conclusion: Radioresistant cells established by fractionated irradiation display CSC-like cell properties. Ad/TRAIL-E1 preferentially targets radioresistant CSC-like cells.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Treatment of Radioresistant Stem-Like Esophageal Cancer Cells by an Apoptotic Gene-Armed, Telomerase-Specific Oncolytic Adenovirus

Zhang

Komaki

Wang

et al. 2008

Clinical Cancer Research

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“…CAR is highly expressed during rodent embryogenesis, especially in the developing brain, but its expression significantly decreases after birth (Johansson et al 1999, Nalbantoglu et al 1999, Honda et al 2000, Ito et al 2000, Tomko et al 2000, Carson 2001). In fact, CAR is found to be involved in neuronal stem cell niche formation via its function as a tight junction component (Hauwel et al 2005). CAR has often been described in homotypic intercellular adhesion, particularly in tight junctions (Coyne et al 2004, Philipson & Pettersson 2004, Coyne & Bergelson 2005).…”

Section: Introductionmentioning

confidence: 99%

CAR expression in human embryos and hESC illustrates its role in pluripotency and tight junctions

Krivega¹,

Geens²,

Velde³

2014

Reproduction

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Coxsackie virus and adenovirus receptor, CXADR (CAR), is present during embryogenesis and is involved in tissue regeneration, cancer and intercellular adhesion. We investigated the expression of CAR in human preimplantation embryos and embryonic stem cells (hESC) to identify its role in early embryogenesis and differentiation. CAR protein was ubiquitously present during preimplantation development. It was localised in the nucleus of uncommitted cells, from the cleavage stage up to the precursor epiblast, and corresponded with the presence of soluble CXADR3/7 splice variant. CAR was displayed on the membrane, involving in the formation of tight junction at compaction and blastocyst stages in both outer and inner cells, and CAR corresponded with the full-length CAR-containing transmembrane domain. In trophectodermal cells of hatched blastocysts, CAR was reduced in the membrane and concentrated in the nucleus, which correlated with the switch in RNA expression to the CXADR4/7 and CXADR2/7 splice variants. The cells in the outer layer of hESC colonies contained CAR on the membrane and all the cells of the colony had CAR in the nucleus, corresponding with the transmembrane CXADR and CXADR4/7. Upon differentiation of hESC into cells representing the three germ layers and trophoblast lineage, the expression of CXADR was downregulated. We concluded that CXADR is differentially expressed during human preimplantation development. We described various CAR expressions: i) soluble CXADR marking undifferentiated blastomeres; ii) transmembrane CAR related with epithelial-like cell types, such as the trophectoderm (TE) and the outer layer of hESC colonies; and iii) soluble CAR present in TE nuclei after hatching. The functions of these distinct forms remain to be elucidated.

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“…This molecule has proven to be an attractive target for adenovirus based gene therapy, but the true function of CAR is only starting to emerge. 76,77 CAR has been shown to play a crucial role in embryogenesis mediating survival signals between cardiomyocytes during heart development. 78 Recent reports have highlighted the potential complexity of CAR function in homophilic interactions at intercellular junctions as well as heterophilic interactions with JAML and JAM-C (Figure 2).…”

Section: The Jam-related Proteinsmentioning

confidence: 99%

JAM Family and Related Proteins in Leukocyte Migration (Vestweber Series)

Bradfield

Nourshargh

Aurrand-Lions

et al. 2007

ATVB

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Abstract-Exploring the role of junctional adhesion molecules (JAMs) has proven to be varied and controversial. The purpose of this review is to discuss the new and exciting roles of these IgSF molecules and how they have evolved to contribute to diverse functions from development to inflammation. In particular, recent research has focused on JAM subfamily members JAM-A, -B, and -C with newly described roles in leukocyte trafficking during inflammation and angiogenesis. However, research on all JAM family members has demonstrated recurring themes with striking similarities in the many diverse processes they are now known to regulate. (Arterioscler Thromb Vasc Biol. 2007;27:2104-2112.)

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Molecular and cellular insights into the coxsackie–adenovirus receptor: role in cellular interactions in the stem cell niche

Cited by 23 publications

References 63 publications

Treatment of Radioresistant Stem-Like Esophageal Cancer Cells by an Apoptotic Gene-Armed, Telomerase-Specific Oncolytic Adenovirus

Treatment of Radioresistant Stem-Like Esophageal Cancer Cells by an Apoptotic Gene-Armed, Telomerase-Specific Oncolytic Adenovirus

CAR expression in human embryos and hESC illustrates its role in pluripotency and tight junctions

JAM Family and Related Proteins in Leukocyte Migration (Vestweber Series)

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