Cytomegalovirus‐associated stage 4S neuroblastoma relapsed stage 4

Nigro, Giovanni; Schiavetti, Amalia; Booth, James C.; Clerico, Aldo; Dominici, Carlo; Krzysztofiak, Andrzej; Castello, Manuel A.

doi:10.1002/mpo.2950240311

Cited by 18 publications

(20 citation statements)

References 16 publications

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“…Viral DNA replication frequently is reactivated from latency, and results in recurrent infection and virus shedding. HCMV infection has been associated with the oncogenesis of some tumors such as Wilms' Tumor and neuroblastoma (34,41). The role of HCMV in the development and clinical course of these tumors has not been completely understood.…”

Section: Discussionmentioning

confidence: 99%

Human Cytomegalovirus (HCMV) IE1 Plays Role in Resistance to Apoptosis with Etoposide in Cancer Cell Line by Cdk2 Accumulation

Kim

Kwon

Park

et al. 2003

Microbiology and Immunology

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Human cytomegalovirus (HCMV) has many strategies to survive the attack of the host. HCMV infection of host cells induces cellular activation and disturbance of the cell cycle. It is possible that HCMV modulates the behavior of certain cancer cells that are susceptible to HCMV infection. This study was performed to identify the possible mechanism of resistance to apoptotic stimuli in some cancer cell lines by HCMV infection. HCMV‐infected cancer cells showed resistance to apoptosis induced by the topoisomerase II inhibitor etoposide. UMG1–2, which constitutively expresses HCMV immediate‐early protein‐1 (IE1), had resistance to apoptosis induced by etoposide as compared with the parental cell line U373MG. Measurement of caspases activity with fluorogenic substrates in etoposide‐treated U373MG and UMG1–2 cells and the direct activation of caspase‐3 with peptides containing arginine‐glycine‐aspartate in U373MG and UMG1–2 cells revealed that the inhibition level of apoptosis by HCMV IE1 would be upstream of caspase‐3 in the caspase cascade pathway. Cellular expression of Cdk2 was increased in UMG1–2 after etoposide treatment while the expression of E2F‐1 in UMG1–2 was decreased as compared with that in U373MG. The Cdk2 inhibitor, roscovitine, decreased the resistance to apoptosis on etoposide‐treated UMG1–2. These results suggest that aberrant HCMV infection confers resistance to anticancer drugs on some cancer cells and protects cells from apoptosis, possibly due to the deregulation of cyclin‐dependent kinase by HCMV immediate‐early protein.

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Section: Discussionmentioning

confidence: 99%

Human Cytomegalovirus (HCMV) IE1 Plays Role in Resistance to Apoptosis with Etoposide in Cancer Cell Line by Cdk2 Accumulation

Kim

Kwon

Park

et al. 2003

Microbiology and Immunology

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“…In developing mice, indeed, mCMV was found to alter cortical neuronal migration (30), and in humans, epilepsy and disorders of cortical development in children with HCMV congenital infection have been described (31). On the other hand, by the induction of drug resistance and alteration of programmed cell death, cytomegalovirus infection may be implicated in the etiology and/or progression of malignancies such as neuroblastoma (4,32). More generally, we hypothesize that all the viruses of the ␤-herpes family known to induce the inhibition of apoptosis, such as herpes simplex virus type 1, Epstein-Barr virus, and CMV, share the same capacity of up-regulating either ⌬N-p73␣ or the other homologous protein ⌬N-p63␣ (33) and that these viral infections are one of the major causes of drug resistance in cancer.…”

Section: Discussionmentioning

confidence: 99%

Human Cytomegalovirus Induces Drug Resistance and Alteration of Programmed Cell Death by Accumulation of ΔN-p73α

Allart¹,

Martin²,

Détraves³

et al. 2002

Journal of Biological Chemistry

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Intrauterine transmission of human cytomegalovirus (HCMV) to the fetus following primary infection in early and late pregnancy usually results in severe neurological handicaps and sensorineural hearing loss with typical migrational anomalies, optic atrophy, disturbed myelination, cerebella hypoplasia, microcephaly, hydrocephaly, and lissencephaly. Recently, evidences raised from the phenotype of p73-deficient mice show that an association may exist between the expression of the TP53 homologous gene and HCMV tropism in the brain, suggesting an implication of p73 in viral persistence. In this study, we demonstrated that HCMV-mediated inhibition of apoptosis only occurs in p73-expressing cells. Upon infection, an accumulation of ⌬N-p73␣ isoforms was observed in HCMV-infected p73-positive cells. This phenomenon was shown to be responsible for the subsequent acquired resistance to apoptosis of infected cells. Inhibition of apoptosis in p73-positive cells by HCMV may thus contribute both to virus persistency and abnormal nervous cell survival. This finding provides the first molecular basis for HCMV-associated abnormal embryonic development and neurological defects in newborns.Human cytomegalovirus (HCMV), 1 a ␤-herpes virus, is harmless to most immunocompetent people. However, HCMV is responsible for serious illness and death in immunocompromised hosts such as AIDS patients, as well as patients receiving immunosuppressive treatment following organ transplantation. Cytomegalovirus infection is the most common congenital viral infection and carries a high risk of long term morbidity and mortality. Intrauterine transmission to the unprotected fetus in early and late pregnancy usually results in death or in severe neurological defects including sensorineural hearing loss, optic atrophy, disturbed myelination, cerebella hypoplasia, microcephaly, hydrocephaly, and lissencephaly (for reviews, see Refs. 1 and 2). How morphological and functional disorders develop is unclear since little is known about mechanisms underlying the pathogenicity of the virus.Apoptosis is an important process participating in the formation of organs and tissues during embryogenesis and in the clearance of abnormal or misfunctioning cells in the body. At any stages of life, interference with this process is predicted to be damaging for organisms. In the mouse developing brain, surprisingly, murine cytomegalovirus (mCMV) was found to induce apoptosis in non-infected cells, whereas a blocking of apoptosis occurred in infected mature neurons (3). Similar results were obtained with human neuroblastoma cells, which become "immortalized" and resistant to cytotoxic stress following HCMV infection (4). As with many other viruses, HCMV has developed strategies to inhibit apoptosis of infected cells, thus escaping from immune clearance, promoting abnormal cell survival, and favoring viral persistence. Some reports discuss possible mechanisms by which HCMV can block apoptosis. HCMV proteins can directly interact with the tumor suppressor p53 and interfere wit...

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“…Neuroblastoma, a paediatric cancer entity, has been associated with increased HCMV antibody titres [56,57]. We analysed 12 tumour samples from neuroblastoma patients carrying N-mycampliWed tumours by reverse transcriptase PCR and detected HCMV IE expression in four samples (Fig.…”

mentioning

confidence: 99%

Oncomodulation by human cytomegalovirus: novel clinical findings open new roads

Michaelis

Baumgarten

Mittelbronn

et al. 2010

Med Microbiol Immunol

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The question whether human cytomegalovirus may affect cancer diseases has been discussed (very controversially) for decades. There are convinced believers and strict opponents of the idea that HCMV might be able to play a role in the course of cancer diseases. In parallel, the number of published reports on the topic is growing. Recently published and presented (Ranganathan P, Clark P, Kuo JS, Salamat S, Kalejta RF. A Survey of Human Cytomegalovirus Genomic Loci Present in Glioblastoma Multiforme Tissue Samples. 35th Annual International Herpes Workshop, Salt Lake City, 2010) data on HCMV detection in glioblastoma tissues and colocalisation of HCMV proteins with cellular proteins known to be relevant for glioblastoma progression motivated us to recapitulate the current state of evidence.

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Cytomegalovirus‐associated stage 4S neuroblastoma relapsed stage 4

Cited by 18 publications

References 16 publications

Human Cytomegalovirus (HCMV) IE1 Plays Role in Resistance to Apoptosis with Etoposide in Cancer Cell Line by Cdk2 Accumulation

Human Cytomegalovirus (HCMV) IE1 Plays Role in Resistance to Apoptosis with Etoposide in Cancer Cell Line by Cdk2 Accumulation

Human Cytomegalovirus Induces Drug Resistance and Alteration of Programmed Cell Death by Accumulation of ΔN-p73α

Oncomodulation by human cytomegalovirus: novel clinical findings open new roads

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