Enhanced nectin-1 expression and herpes oncolytic sensitivity in highly migratory and invasive carcinoma Journal Article
| Authors: | Yu, Z.; Chan, M. K.; O-Charoenrat, P.; Eisenberg, D. P.; Shah, J. P.; Singh, B.; Fong, Y.; Wong, R. J. |
| Article Title: | Enhanced nectin-1 expression and herpes oncolytic sensitivity in highly migratory and invasive carcinoma |
| Abstract: | Purpose: Although a variety of malignant tumors are susceptible to therapy with oncotytic herpes simplex viruses, the determinants of tumor sensitivity to these viruses are poorly understood. Nectin-1 is a cell surface adhesion molecule that is a component of intercellular adherens junctions and also functions as a herpes viral receptor. Because highly invasive cells may have decreased intercellular adhesion, we sought to determine if such cells might also have altered availability of cell surface nectin-1 to act as a herpes receptor. Experimental Design and Results: A series of squamous cell carcinoma lines of increasing migratory and invasive potential, termed MG1-MG14, were selected by serial passages of murine SCC7 through Matrigel invasion chambers. Available cell surface nectin-1 was enhanced on the MG11 and MG14 cell lines in comparison to SCC7 as measured by cellular ELISA and immunofluorescence microscopy. A replication-competent, oncolytic herpes virus (NV1023) showed an increased ability to enter MG11 and MG14 cells as compared with SCC7 cells. Furthermore, MG11 and MG14 supported increased herpes viral replication and cytotoxicity over SCC7. For all three of the cell lines, viral entry assays revealed that the actively migrating cells were significantly more susceptible to herpes infection than the nonmigrating cells. Conclusions: These results show that malignant cells with highly migratory and invasive properties may exhibit increased cell surface nectin-1 availability, which may serve as a herpes viral receptor to enhance the efficacy of herpes oncolytic therapy. This finding has implications regarding patient selection for future clinical trials using these promising therapeutic vectors. © 2005 American Association for Cancer Research. |
| Keywords: | controlled study; protein expression; unclassified drug; squamous cell carcinoma; carcinoma, squamous cell; nonhuman; cell proliferation; animal cell; mouse; animals; cell survival; cell line; cytotoxicity; cell line, tumor; cercopithecus aethiops; cancer therapy; enzyme linked immunosorbent assay; time factors; virus receptor; fluorescent antibody technique; oncolytic virus; simplexvirus; cell migration; cell movement; malignant neoplastic disease; cell adhesion molecules; invasive carcinoma; neoplasm invasiveness; matrigel; virus replication; enzyme-linked immunosorbent assay; cell junction; cell adhesion; herpes simplex virus; cell invasion; vero cells; immunofluorescence microscopy; cell adhesion molecule; virus vector; cell surface; virus cell interaction; nectin 1; cell strain mg1; cell strain mg2; cell strain mg3; cell strain mg4; cell strain scc7 |
| Journal Title: | Clinical Cancer Research |
| Volume: | 11 |
| Issue: | 13 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2005-07-01 |
| Start Page: | 4889 |
| End Page: | 4897 |
| Language: | English |
| DOI: | 10.1158/1078-0432.ccr-05-0309 |
| PUBMED: | 16000587 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 18" - "Export Date: 24 October 2012" - "CODEN: CCREF" - "Source: Scopus" |
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