Nectin-1 expression by squamous cell carcinoma is a predictor of herpes oncolytic sensitivity Journal Article
| Authors: | Yu, Z.; Adusumilli, P. S.; Eisenberg, D. P.; Darr, E.; Ghossein, R. A.; Li, S.; Liu, S.; Singh, B.; Shah, J. P.; Fong, Y.; Wong, R. J. |
| Article Title: | Nectin-1 expression by squamous cell carcinoma is a predictor of herpes oncolytic sensitivity |
| Abstract: | Oncolytic viruses based on herpes simplex virus type 1 (HSV-1) are able to infect and lyse a variety of malignant cell lines. However, there is variability in the degree of tumor susceptibility, and the cancer cell determinants of HSV sensitivity are poorly defined. Nectin-1 is a cell surface adhesion molecule that functions as a cellular receptor to HSV envelope glycoprotein D (gD). We assessed tumor nectin-1 expression as a predictor of oncolytic HSV sensitivity. A panel of human squamous carcinoma cell lines was evaluated for viral entry, replication, and cytotoxicity to an attenuated, replication-competent, oncolytic HSV (NV1023). Potential tumor determinants of HSV sensitivity were assessed, including nectin-1, herpes viral entry mediator, total gD receptor expression, S-phase fraction, and doubling time. Significant correlations between nectin-1 expression measured by quantitative fluorescence-activated cell sorting and viral sensitivity measures were identified using Pearson's coefficients. Cancer cell nectin-1 receptor blockade and nectin-1 transfection led to inhibition and enhancement of NV1023 viral entry, respectively. Cell lines with varying nectin-1 expression showed corresponding sensitivity to NV1023 therapy in vivo. Immunohistochemistry for nectin-1 was inversely related to E-cadherin staining, suggesting increased herpes sensitivity of E-cadherin-deficient tumors. These results suggest that nectin-1 may be used as a marker to predict the sensitivity of a tumor to herpes oncolytic therapy. |
| Keywords: | immunohistochemistry; controlled study; protein expression; human cell; squamous cell carcinoma; carcinoma, squamous cell; nonhuman; sensitivity and specificity; mouse; animals; mice; animal tissue; cell cycle s phase; animal experiment; animal model; herpes simplex; in vivo study; cancer cell culture; cytotoxicity; xenograft model antitumor assays; cell line, tumor; uvomorulin; cancer therapy; prediction; time; cell transformation, neoplastic; gene expression regulation, neoplastic; correlation analysis; correlation coefficient; genetic transfection; mice, nude; quantitative analysis; gene therapy; oncolytic virus; simplexvirus; oncolytic viruses; oncolytic virotherapy; cell adhesion molecules; herpesvirus 1, human; experimental neoplasm; virus replication; receptor blocking; cadherins; fluorescence activated cell sorting; herpes simplex virus 1; herpes; s phase; infection sensitivity; transgenes; cell adhesion molecule; cricetinae; virus attenuation; receptor protein; virus cell interaction; human herpesvirus 1; viral envelope proteins; glycoprotein d; nectin 1; virus internalization; receptors, tumor necrosis factor, member 14 |
| Journal Title: | Molecular Therapy |
| Volume: | 15 |
| Issue: | 1 |
| ISSN: | 1525-0016 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2007-01-01 |
| Start Page: | 103 |
| End Page: | 113 |
| Language: | English |
| DOI: | 10.1038/sj.mt.6300009 |
| PUBMED: | 17164781 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 16" - "Export Date: 17 November 2011" - "CODEN: MTOHC" - "Source: Scopus" |
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