Brief report: Nectin-1 is a marker of thyroid cancer sensitivity to herpes oncolytic therapy Journal Article
| Authors: | Huang, Y. Y.; Yu, Z.; Lin, S. F.; Li, S.; Fong, Y.; Wong, R. J. |
| Article Title: | Brief report: Nectin-1 is a marker of thyroid cancer sensitivity to herpes oncolytic therapy |
| Abstract: | Context: The prognosis for patients diagnosed with anaplastic thyroid cancer is dismal, with a median survival time of only 6 months. Novel therapies are needed for these and other thyroid cancers that are refractory to conventional therapy. Objectives: Our goals were to assess the ability of an attenuated, replication-competent, oncolytic herpes virus (NV1023) to enter and lyse human thyroid cancers and determine whether herpes simplex virus receptor expression is a determinant of NV1023 efficacy. Design: A panel of 12 human thyroid cancer cell lines including anaplastic, medullary, follicular, and papillary cancers were exposed to NV1023 and assessed for susceptibility to viral entry and oncolysis. The expression of herpes simplex virus glycoprotein D receptors nectin-1 and herpes virus entry mediator was assessed by quantitative fluorescence-activated cell sorter and correlated with NV1023 entry and oncolysis. Results: There was significant variation in the ability of NV1023 to enter thyroid cancer cells as measured by lacZ expression. Thyroid cancer nectin-1 expression correlated strongly with NV1023 entry. Nectin-1 transfections and antibody receptor blocking studies validated the importance of nectin-1 for NV1023 entry. Follicular cancers were least sensitive to NV1023 oncolysis. All anaplastic, medullary, and papillary cancers tested exhibited greater than 85% cytotoxicity 7 d after exposure to NV1023 at multiplicity of infection 1, although oncolysis was variable at multiplicity of infection 0.01. Significant correlations between nectin-1 expression and NV1023 oncolysis were identified using Pearson's coefficients. Conclusions: NV1023 causes significant cytotoxicity of anaplastic, medullary, and papillary thyroid cancers. Nectin-1 is a novel marker of thyroid cancer sensitivity to herpes oncolytic therapy that might guide patient selection for therapy. Copyright © 2007 by The Endocrine Society. |
| Keywords: | controlled study; protein expression; unclassified drug; human cell; genetics; flow cytometry; animal; metabolism; animals; cancer susceptibility; fluorescence; tumor markers, biological; cancer cell culture; cytotoxicity; cell line, tumor; transfection; tumor marker; correlation coefficient; genetic transfection; tumor cell line; oncolytic herpes virus; herpesviridae; simplexvirus; oncolytic virotherapy; heparin; cell adhesion molecules; herpesvirus 1, human; thyroid cancer; thyroid neoplasms; papillary carcinoma; herpes simplex virus 1; herpes; thyroid tumor; anaplastic carcinoma; herpesvirus entry mediator; medullary carcinoma; cell adhesion molecule; follicular carcinoma; cho cell; cho cells; cricetinae; cricetulus; hamster; viral envelope proteins; nectin 1; nectins; virus envelope protein; cell sorter; receptors, tumor necrosis factor, member 14 |
| Journal Title: | Journal of Clinical Endocrinology and Metabolism |
| Volume: | 92 |
| Issue: | 5 |
| ISSN: | 0021-972X |
| Publisher: | Oxford University Press |
| Date Published: | 2007-05-01 |
| Start Page: | 1965 |
| End Page: | 1970 |
| Language: | English |
| DOI: | 10.1210/jc.2007-0040 |
| PUBMED: | 17327376 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 7" - "Export Date: 17 November 2011" - "CODEN: JCEMA" - "Source: Scopus" |
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