Reovirus oncolysis in human head and neck squamous carcinoma cells

Ikeda, Yoichi; Nishimura, Goushi; Yanoma, Syunsuke; Kubota, Akira; Furukawa, Madoka; Tsukuda, Mamoru

doi:10.1016/s0385-8146(04)00111-7

Cited by 24 publications

(14 citation statements)

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“…Oncolytic viruses can potentially induce tumour cell death through cell lysis secondary to overwhelming replicating viral burden, 29 through virus-induced apoptosis, 7 or through a combination of the two. Both lytic (that is, necrotic) and apoptotic cell death have been shown, when associated with induction of appropriate immune 'danger signals', to be capable of priming effective anti-tumour immunity.…”

Section: Mode Of Tumour Cell Death Following Reovirus Infectionmentioning

confidence: 99%

Inflammatory tumour cell killing by oncolytic reovirus for the treatment of melanoma

et al. 2008

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Reovirus is a promising unmodified double-stranded RNA (dsRNA) anti-cancer oncolytic virus, which is thought to specifically target cells with activated Ras. Although reovirus has been tested in a wide range of preclinical models and has entered early clinical trials, it has not previously been tested for the treatment of human melanoma. Here, we show that reovirus effectively kills and replicates in both human melanoma cell lines and freshly resected tumour; intratumoural injection also causes regression of melanoma in a xenograft in vivo model. Reovirus-induced melanoma death is blocked by caspase inhibition and is dependent on constituents of the Ras/RalGEF/p38 pathway. Reovirus melanoma killing is more potent than, and distinct from, chemotherapy or radiotherapy-induced cell death; a range of inflammatory cytokines and chemokines are released by infected tumour cells, while IL-10 secretion is abrogated. Furthermore, the inflammatory response generated by reovirus-infected tumour cells causes bystander toxicity against reovirus-resistant tumour cells and activates human myeloid dendritic cells (DC) in vitro. Hence, reovirus is suitable for clinical testing in melanoma, and may provide a useful danger signal to reverse the immunologically suppressive environment characteristic of this tumour.

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Section: Mode Of Tumour Cell Death Following Reovirus Infectionmentioning

confidence: 99%

Inflammatory tumour cell killing by oncolytic reovirus for the treatment of melanoma

et al. 2008

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“…[15][16][17] Other groups have reported that reoviral oncolysis is associated with induction of apoptosis in various cancer types, 18 using signaling molecules such as TNF-related apoptosis-inducing ligand (TRAIL), 19 caspase 8 and JNK MAPK. 20 YC-1, 3-(5 0 -hydroxymethy-2 0 -furyl)-1-benzylindazole, was originally identified as a potential therapeutic drug for circulatory disorders, as it is able to inhibit platelet aggregation and vascular contraction by activating soluble guanylyl cyclase.…”

Section: Introductionmentioning

confidence: 99%

Down-regulation of HIF-1α by oncolytic reovirus infection independently of VHL and p53

et al. 2010

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Many oncolytic viruses are currently being tested as potential cancer therapeutic agents. To be effective, these viruses must replicate and propagate efficiently through the tumor mass. However, it is possible that the hypoxia that characterizes many tumors may be an obstacle to viral therapy because of its inhibition of viral replication and propagation. We, therefore, decided to test how oncolytic reovirus and its target cells respond to hypoxia. We found that reovirus infection suppresses hypoxia inducible factor (HIF)-1a protein levels (but not transcript abundance) in colon cancer HCT116 cells under CoCl 2 or hypoxia. Reovirus infection was able to reduce HIF-1a levels in both von Hippel Lindau (VHL)À/À renal carcinoma A498 and p53À/À HCT116 cells, indicating that the decrease of HIF-1a mediated by reovirus requires neither VHL nor p53 proteins. However, treatment with the inhibitor MG132 restored HIF-1a levels, suggesting that reovirus-induced HIF-1a decrease needs proteosomal activity. A498 VHLÀ/À cells with constitutive expression of HIF-1a were relatively resistant to reovirus-induced apoptosis when compared with A498 VHL þ / þ cells. However, we found that the use of YC-1 to target HIF-1a promoted reovirus-induced apoptosis in A498 VHLÀ/À cells. Accordingly, we propose that reovirus may be used together with YC-1 as a potential therapeutic agent against chemoresistant or radioresistant tumors that are hypoxic and show increased levels of HIF-1a.

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“…11,14,15 It has also been reported that reoviral oncolysis was associated with the induction of apoptosis in various cancer types. 16 Further investigation has revealed that tumor necrosis factor (TNF)-related apoptosisinducing ligand (TRAIL), a member of the TNF superfamily, is involved in reovirus-induced apoptosis. 17 Caspase 8 and JNK MAPK proteins also participate in apoptotic signaling following reoviral infection.…”

Section: Introductionmentioning

confidence: 99%

CUG2, a novel oncogene confers reoviral replication through Ras and p38 signaling pathway

Park

I-R

et al. 2010

Cancer Gene Ther

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As we have recently found a novel oncogene, the cancer-upregulated gene 2 (CUG2), which was elevated in a variety of tumor tissues such as the ovary, liver, lung and pancreas, we examined whether reovirus could efficiently induce cytolysis in cancer cells expressing CUG2 and thus be used as a potential cancer therapeutic agent. In this study, we describe experiments in which we use reovirus to treat NIH3T3 cells stably expressing either CUG2 (NIH-CUG2) or vector only (NIH-Vec). NIH-CUG2 cells readily support reoviral proliferation and undergo apoptosis, whereas NIH-Vec cells are highly resistant to reoviral infection and virusinduced apoptosis. This notable result may be explained by the observation that CUG2 expression inhibits PKR activation, leading to reoviral proliferation in nonpermissive NIH3T3 cells. Furthermore, reovirus infection results in almost complete regression of tumorgenic NIH-CUG2 cells in transplanted nude mice. As we found that CUG2 enhances activation of MAPK (ERK, JNK and p38), Src kinase and Ras, we examined whether CUG2 confers reoviral replication independent of the Ras or p38 MAPK signaling pathway. From these experiments we found that either inhibition of p38 MAPK or Ras blocks reoviral proliferation even in the presence of CUG2 but inhibition of ERK, JNK and Src kinase does not, indicating that activation of p38 MAPK and Ras has critical roles in reoviral replication in CUG2-expressing tumor cells. Accordingly, we propose that reovirus can be useful in the treatment of transformed cells expressing CUG2, which is commonly detected in various tumor tissues.

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Reovirus oncolysis in human head and neck squamous carcinoma cells

Cited by 24 publications

References 0 publications

Inflammatory tumour cell killing by oncolytic reovirus for the treatment of melanoma

Inflammatory tumour cell killing by oncolytic reovirus for the treatment of melanoma

Down-regulation of HIF-1α by oncolytic reovirus infection independently of VHL and p53

CUG2, a novel oncogene confers reoviral replication through Ras and p38 signaling pathway

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