Nectin-1 expression by squamous cell carcinoma is a predictor of herpes oncolytic sensitivity

Mol Ther. 2007 Jan;15(1):103-13. doi: 10.1038/


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cadherins / metabolism
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / therapy
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism*
  • Cell Line, Tumor
  • Cell Transformation, Neoplastic*
  • Cricetinae
  • Gene Expression Regulation, Neoplastic / genetics*
  • Genetic Therapy
  • Herpesvirus 1, Human / physiology*
  • Humans
  • Immunohistochemistry
  • Mice
  • Mice, Nude
  • Nectins
  • Oncolytic Viruses / physiology*
  • Receptors, Tumor Necrosis Factor, Member 14 / metabolism
  • S Phase
  • Sensitivity and Specificity
  • Transgenes / genetics
  • Viral Envelope Proteins / metabolism
  • Virus Internalization
  • Xenograft Model Antitumor Assays


  • Cadherins
  • Cell Adhesion Molecules
  • NECTIN1 protein, human
  • Nectin1 protein, mouse
  • Nectins
  • Receptors, Tumor Necrosis Factor, Member 14
  • Viral Envelope Proteins