Journal article
Herpes Simplex Virus Type 1 Preferentially Targets Human Colon Carcinoma: Role of Extracellular Matrix
Journal of virology, Vol.82(2), pp.999-1010
01/2008
DOI: 10.1128/JVI.01769-07
PMCID: PMC2224594
PMID: 17977977
Abstract
Viral therapy of cancer (viral oncolysis) is dependent on selective destruction of the tumor tissue compared with healthy tissues. Several factors, including receptor expression, extracellular components, and intracellular mechanisms, may influence viral oncolysis. In the present work, we studied the potential oncolytic activity of herpes simplex virus type 1 (HSV-1), using an organ culture system derived from colon carcinoma and healthy colon tissues of mouse and human origin. HSV-1 infected normal colons ex vivo at a very low efficiency, in contrast to high-efficiency infection of colon carcinoma tissue. In contrast, adenoviral and lentiviral vectors infected both tissues equally well. To investigate the mechanisms underlying the preferential affinity of HSV-1 for the carcinoma tissue, intracellular and extracellular factors were investigated. Two extracellular components, collagen and mucin molecules, were found to restrict HSV-1 infectivity in the healthy colon. The mucin layer of the healthy colon binds to HSV-1 and thereby blocks viral interaction with the epithelial cells of the tissue. In contrast, colon carcinomas express small amounts of collagen and mucin molecules and are thus permissive to HSV-1 infection. In agreement with the ex vivo system, HSV-1 injected into a mouse colon carcinoma in vivo significantly reduced the volume of the tumor. In conclusion, we describe a novel mechanism of viral selectivity for malignant tissues that is based on variance of the extracellular matrix between tumor and healthy tissues. These insights may facilitate new approaches to the application of HSV-1 as an oncolytic virus.
Details
- Title: Subtitle
- Herpes Simplex Virus Type 1 Preferentially Targets Human Colon Carcinoma: Role of Extracellular Matrix
- Creators
- Dror Kolodkin-Gal - Department of Virology, The Hebrew University, Hadassah Medical School, Jerusalem, IsraelGideon Zamir - Department of Virology, The Hebrew University, Hadassah Medical School, Jerusalem, IsraelYair Edden - Department of Virology, The Hebrew University, Hadassah Medical School, Jerusalem, IsraelEli Pikarsky - Department of Virology, The Hebrew University, Hadassah Medical School, Jerusalem, IsraelAlon Pikarsky - Department of Virology, The Hebrew University, Hadassah Medical School, Jerusalem, IsraelHillel Haim - Department of Virology, The Hebrew University, Hadassah Medical School, Jerusalem, IsraelYosef S Haviv - Department of Virology, The Hebrew University, Hadassah Medical School, Jerusalem, IsraelAmos Panet - Department of Virology, The Hebrew University, Hadassah Medical School, Jerusalem, Israel
- Resource Type
- Journal article
- Publication Details
- Journal of virology, Vol.82(2), pp.999-1010
- DOI
- 10.1128/JVI.01769-07
- PMID
- 17977977
- PMCID
- PMC2224594
- NLM abbreviation
- J Virol
- ISSN
- 0022-538X
- eISSN
- 1098-5514
- Publisher
- American Society for Microbiology (ASM)
- Language
- English
- Date published
- 01/2008
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984083881702771
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