RRC ID 42277
Author Kamiyama H, Kurosaki K, Kurimoto M, Katagiri T, Nakamura Y, Kurokawa M, Sato H, Endo S, Shiraki K.
Title Herpes simplex virus-induced, death receptor-dependent apoptosis and regression of transplanted human cancers.
Journal Cancer Sci
Abstract Inoculation of a live attenuated herpes simplex virus (HSV) vector, betaH1, into human U87MG glioblastoma cells transplanted into athymic nude mice induced complete regression of tumors. The infected cells underwent histochemically confirmed apoptosis without lymphocyte infiltration after expressing CD30, CD30 ligand (CD30L), tumor necrosis factor (TNF)-alpha, TNF receptor 1 (TNF-R1), FAS, and FAS ligand (FAS-L) with activation of caspases 3 and 8. Induction of the transcripts of these receptors and ligands in inoculated tumors was confirmed by quantitative RT-PCR. To examine the specificity of apoptosis in the transplanted tumor, we inoculated betaH1 into transplanted human lung, breast, gastric, and colon cancer tumors, and similar tumor regression with apoptosis was observed in all tumors. We analyzed the roles of expression of CD30, CD30L, TNF-alpha, TNF-R1, FAS, and FAS-L in the tumors, and found that HSV-induced apoptosis was suppressed by the respective antibodies. These findings indicate that the CD30/CD30L, TNF-alpha/TNF-R1, and FAS/FAS-L interactions resulted in apoptosis and tumor regression in immunocompromised mice. In addition to the death receptor-dependent apoptosis induced by HSV, the expressed ligands and receptors might enhance the susceptibility of tumor cells to cell-mediated cyto-toxicity and augment the activation of tumor-killing lymphocytes in immunocompetent models.
Volume 95(12)
Pages 990-8
Published 2004-12-1
DOI 10.1111/j.1349-7006.2004.tb03188.x
PMID 15596049
MeSH Animals Apoptosis* Breast Neoplasms / metabolism Breast Neoplasms / pathology Breast Neoplasms / virology CD30 Ligand Caspase 3 Caspase 8 Caspases / metabolism Colonic Neoplasms / metabolism Colonic Neoplasms / pathology Colonic Neoplasms / virology Enzyme Activation Fas Ligand Protein Glioblastoma / metabolism* Glioblastoma / pathology Glioblastoma / virology Herpes Simplex / metabolism* Herpes Simplex / pathology Herpes Simplex / virology Herpesvirus 1, Human / physiology* Humans Ki-1 Antigen / metabolism Lung Neoplasms / metabolism Lung Neoplasms / pathology Lung Neoplasms / virology Male Membrane Glycoproteins / metabolism Mice Mice, Inbred BALB C Mice, Nude Receptors, Tumor Necrosis Factor, Type I / metabolism Stomach Neoplasms / metabolism Stomach Neoplasms / pathology Stomach Neoplasms / virology Tumor Necrosis Factor-alpha / metabolism Virus Replication fas Receptor / metabolism
IF 4.966
Times Cited 4
Human and Animal Cells A549(RCB0098)