This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Huang, Y.-Y. Articles by Wong, R. J. Search for Related Content PubMed PubMed Citation Articles by Huang, Y.-Y. Articles by Wong, R. J. Related Collections Thyroid Endocrine Oncology

Nectin-1 Is a Marker of Thyroid Cancer Sensitivity to Herpes Oncolytic Therapy

Head and Neck Service (Y.-Y.H., Z.Y., S.-F.L., S.L., R.J.W.) and Gastric and Mixed Tumor Service (Y.F.), Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10021; and Division of Endocrinology and Metabolism (Y.-Y.H., S.-F.L.), Chang Gung Memorial Hospital, Chang Gung University, Taipei, Taiwan

Address all correspondence and requests for reprints to: Richard J. Wong, M.D., Head and Neck Service, C-1069, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021. E-mail: wongr{at}mskcc.org.

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.

This article has been cited by other articles:

				S. Libertini, I. Iacuzzo, G. Perruolo, S. Scala, C. Ierano, R. Franco, G. Hallden, and G. Portella Bevacizumab Increases Viral Distribution in Human Anaplastic Thyroid Carcinoma Xenografts and Enhances the Effects of E1A-Defective Adenovirus dl922-947 Clin. Cancer Res., October 15, 2008; 14(20): 6505 - 6514. [Abstract] [Full Text] [PDF]

				S.-F. Lin, S. P. Gao, D. L. Price, S. Li, T.-C. Chou, P. Singh, Y.-Y. Huang, Y. Fong, and R. J. Wong Synergy of a Herpes Oncolytic Virus and Paclitaxel for Anaplastic Thyroid Cancer Clin. Cancer Res., March 1, 2008; 14(5): 1519 - 1528. [Abstract] [Full Text] [PDF]