Expression of the coxsackievirus and adenovirus receptor in musculoskeletal tumors and mesenchymal tissues: efficacy of adenoviral gene therapy for osteosarcoma

Kawashima, Hiroyuki; Ogose, Akira; Yoshizawa, Tatsuya; Kuwano, Ryozo; Hotta, Yuko; Hotta, Tomomitsu; Hatano, Hiroshi; Endo, Naoto

doi:10.1111/j.1349-7006.2003.tb01354.x

Cited by 27 publications

(29 citation statements)

References 28 publications

(30 reference statements)

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“…This is consistent with the findings of Kawashima et al, who demonstrated expression of coxsackie-adenovirus receptor (CAR), which is crucial for efficient viral entry into cells, was high in musculoskeletal tumor cell lines and tissue samples. 46 All sarcoma cell lines exhibited a dosedependent decrease in cell viability when treated with Adwtp53 but not with Ad-mutp53. These results indicate that it is the gene product of Ad-wtp53 rather than the viral vector itself that is cytotoxic.…”

Section: Discussionmentioning

confidence: 93%

“…This could be attributed to lower efficiency of infection from low expression of the CAR receptor. 46 Figure 1b shows the morphologic changes that occur when the sarcoma cell lines are treated with Ad-wtp53. All four cells lines showed evidence of lower cell density, lifting of cells off plate and membrane blebbing, an indication of apoptosis.…”

Section: Effect Of Ad-wtp53 On In Vitro Cell Growthmentioning

confidence: 99%

“…Adenovirus-mediated delivery of p53 as a therapeutic strategy has been investigated in a variety of neoplasms including cervical cancer, 37 ovarian cancer, 38 prostatic cancer, 39 lung cancer, 40 esophageal cancer, 41 nasopharyngeal cancer 42 and squamous cell carcinoma of the head and neck 43 46 In this study, we examined the effect of adenovirusmediated p53 gene transfer in four sarcoma cell lines exhibiting a spectrum of p53 mutation status: two RMS (RD, Rh4), one Ewing's (Rh1) and one UND-STS (A204). We used three viral vectors (courtesy of Dr Phillip Branton, McGill University) containing wild-type p53, mutant (Cys135Ser) p53 and the lacZ reporter gene.…”

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confidence: 99%

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Adenovirus-mediated p53 gene therapy in pediatric soft-tissue sarcoma cell lines: sensitization to cisplatin and doxorubicin

et al. 2004

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Sarcomas, or tumors of connective tissue, represent roughly 20% of childhood cancers. Although the cure rate for sarcomas in general has significantly improved in the last 10 years, there continue to be subgroups that are difficult to treat. High-grade or metastatic soft-tissue sarcomas and rhabdomyosarcomas (RMS) of the extremities remain therapeutic challenges and their prognosis is often poor. The future of sarcoma therapy will likely include molecular approaches including gene/protein expression profiling and gene-based therapy. Most sarcomas harbor defects in the p53 or pRb pathways. The tumor suppressor p53 is central to regulation of cell growth and tumor suppression and restoring wild-type p53 function in pediatric sarcomas may be of therapeutic benefit. Studies with adenoviral-mediated p53 gene transfer have been conducted in many cancer types including cervical, ovarian, prostatic and head and neck tumors. Studies of this approach, however, remain limited in pediatric cancers, including sarcomas. Using three viral constructs containing cDNA for wild-type p53, mutant p53 (C135S) and lacZ, we studied the effect of adenoviralmediated gene therapy in four pediatric sarcoma cell lines, RD and Rh4 (RMS), Rh1 (Ewing's sarcoma) and A204 (undifferentiated sarcoma). Using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay, we have shown a dose-dependent decrease in cell viability 72 h post-treatment that occurs with Ad-wtp53 but not with Ad-mutp53. Cells treated with Ad-wtp53 show upregulation of the p53 downstream targets, p21 CIP1/WAF1 and bax. Growth curves demonstrate suppression of cell growth over a period of 4 days and cells treated with Ad-wtp53 demonstrate a significant increase in sensitivity to the chemotherapeutic agents, cisplatin and doxorubicin. Our results indicate that restoration of wild-type p53 function in pediatric sarcoma cells could provide a basis for novel approaches to treatment of this disease.

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Section: Discussionmentioning

confidence: 93%

Section: Effect Of Ad-wtp53 On In Vitro Cell Growthmentioning

confidence: 99%

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confidence: 99%

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Adenovirus-mediated p53 gene therapy in pediatric soft-tissue sarcoma cell lines: sensitization to cisplatin and doxorubicin

et al. 2004

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“…A strong correlation between the expression of CAR on the cell surface and the level of transgene expression in photochemically treated cells was observed, suggesting that the absolute level of virus binding to the cell surface determines the level of transduction in photochemically treated cells, as reported by other groups for conventional adenoviral infection. [18][19][20] Blocking CAR with recombinant Ad5 fiber-knob resulted in a complete inhibition of gene expression, both in conventionally infected and in photochemically treated cells. These results strengthen the assumption that attachment to the cell surface is a key event for PCI-mediated transduction and suggest further that nonreceptor-mediated uptake pathways are not involved in the photochemical transduction pathway.…”

Section: Discussionmentioning

confidence: 99%

“…Using the RmcB anti-CAR monoclonal antibody, 13 we found that the cell lines used in this study expressed different levels of CAR ( Table 1) Fig 1b), as previously reported by other groups. [18][19][20] The relationship between the expression of CAR and the percentage of b-galactosidasepositive cells in photochemically treated cells showed an even better linear correlation (P ¼ .002 , Fig 1b), suggesting that virus binding to the cell surface is of fundamental importance also for photochemical transduction.…”

Section: Influence Of Car On Photochemical Transductionmentioning

confidence: 99%

PCI-enhanced adenoviral transduction employs the known uptake mechanism of adenoviral particles

et al. 2005

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The development of methods for efficient and specific delivery of therapeutic genes into target tissues is an important issue for further development of in vivo gene therapy. In the present study, the physical targeting technique, photochemical internalization (PCI), has been used together with adenovirus. The combination of PCI and adenoviral transduction has previously been shown to be favorable compared to adenovirus used alone, and the aim of this study was to verify the role of the adenoviral receptors and identify the uptake pathway used by adenoviral particles in photochemically treated cells. All examined cell lines showed augmented transduction efficiency after PCI-treatment, with a maximum of 13-fold increase in transgene expression compared to conventionally infected cells. Blocking of CAR induced a complete inhibition of PCI-enhanced transgene expression. However, photochemical treatment managed to enhance the transduction efficiency of the retargeted virus AdRGD-GFP showing also that the virus-CAR interaction is not vital for obtaining a photochemical effect on adenoviral transduction. Blocking the a V -integrins reduced the gene expression significantly in photochemically treated cells. Subjecting HeLa cells expressing negative mutant-dynamin to light treatment after infection gave no significant increase in gene transfer, while the gene transfer were enhanced seven-fold in cells with wild-type dynamin. Furthermore, chlorpromazine inhibited photochemical transduction in a dose-dependent manner, whereas Filipin III had no effect on the gene transfer. In summary, the data presented imply that adenoviral receptor binding is important and clathrin-mediated endocytosis is the predominant uptake mechanism for adenoviral particles in photochemically treated cells.

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Osteosarcoma cell lines display variable individual reactions on wildtype p53 and Rb tumour‐suppressor transgenes

Hellwinkel

Müller

Pollmann

et al. 2004

The Journal of Gene Medicine

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Expression of the coxsackievirus and adenovirus receptor in musculoskeletal tumors and mesenchymal tissues: efficacy of adenoviral gene therapy for osteosarcoma

Abstract: Recombinant adenovirus is used as a competent vector in a wide

Cited by 27 publications

References 28 publications

Adenovirus-mediated p53 gene therapy in pediatric soft-tissue sarcoma cell lines: sensitization to cisplatin and doxorubicin

Adenovirus-mediated p53 gene therapy in pediatric soft-tissue sarcoma cell lines: sensitization to cisplatin and doxorubicin

PCI-enhanced adenoviral transduction employs the known uptake mechanism of adenoviral particles

Osteosarcoma cell lines display variable individual reactions on wildtype p53 and Rb tumour‐suppressor transgenes

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