title: Nectin-1 is a marker of thyroid cancer sensitivity to herpes oncolytic therapy.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Head and Neck Service, C-1069, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
authors.forename: Yu-Yao
authors.initials: YY
authors.lastname: Huang
authors.forename: Zhenkun
authors.initials: Z
authors.lastname: Yu
authors.forename: Shu-Fu
authors.initials: SF
authors.lastname: Lin
authors.forename: Sen
authors.initials: S
authors.lastname: Li
authors.forename: Yuman
authors.initials: Y
authors.lastname: Fong
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Wong
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor; D016466:CHO Cells; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D006224:Cricetinae; D003412:Cricetulus; D005434:Flow Cytometry; D006493:Heparin / Q000378:metabolism; D018259:Herpesvirus 1, Human / Q000235:genetics*; D006801:Humans; D000075983:Nectins; D050130:Oncolytic Virotherapy; D053240:Receptors, Tumor Necrosis Factor, Member 14 / Q000235:genetics; D013964:Thyroid Neoplasms / Q000378:metabolism* / Q000628:therapy*; D014162:Transfection; D014759:Viral Envelope Proteins / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; C000619010:NECTIN1 protein, human; D000075983:Nectins; D053240:Receptors, Tumor Necrosis Factor, Member 14; D014759:Viral Envelope Proteins; D006493:Heparin