Oncolytic herpes simplex virus kills stem-like tumor-initiating colon cancer cells Journal Article
| Authors: | Warner, S. G.; Haddad, D.; Au, J.; Carson, J. S.; O'Leary, M. P.; Lewis, C.; Monette, S.; Fong, Y. |
| Article Title: | Oncolytic herpes simplex virus kills stem-like tumor-initiating colon cancer cells |
| Abstract: | Stem-like tumor-initiating cells (TICs) are implicated in cancer progression and recurrence, and can be identified by sphere-formation and tumorigenicity assays. Oncolytic viruses infect, replicate in, and kill a variety of cancer cells. In this study, we seek proof of principle that TICs are susceptible to viral infection. HCT8 human colon cancer cells were subjected to serum-free culture to generate TIC tumorspheres. Parent cells and TICs were infected with HSV-1 subtype NV1066. Cytotoxicity, viral replication, and Akt1 expression were assessed. TIC tumorigenicity was confirmed and NV1066 efficacy was assessed in vivo. NV1066 infection was highly cytotoxic to both parent HCT8 cells and TICs. In both populations, cell-kill of >80% was achieved within 3 days of infection at a multiplicity of infection (MOI) of 1.0. However, the parent cells required 2-log greater viral replication to achieve the same cytotoxicity. TICs overexpressed Akt1 in vitro and formed flank tumors from as little as 100 cells, growing earlier, faster, larger, and with greater histologic atypia than tumors from parent cells. Treatment of TIC-induced tumors with NV1066 yielded tumor regression and slowed tumor growth. We conclude that colon TICs are selected for by serum-free culture, overexpress Akt1, and are susceptible to oncolytic viral infection. |
| Keywords: | protein kinase b; controlled study; treatment outcome; unclassified drug; human cell; histopathology; cancer growth; drug efficacy; nonhuman; mouse; animal tissue; gene overexpression; animal experiment; animal model; in vivo study; in vitro study; cancer inhibition; cancer regression; colon cancer; cancer stem cell; carcinogenicity; cancer size; oncolytic herpes virus; oncolytic virotherapy; drug cytotoxicity; virus replication; herpes simplex virus 1; cell killing; colon carcinogenesis; growth rate; nv 1066; protein akt1; human; female; priority journal; article; tumor initiating cell |
| Journal Title: | Molecular Therapy - Oncolytics |
| Volume: | 3 |
| ISSN: | 2372-7705 |
| Publisher: | Cell Press |
| Date Published: | 2016-01-01 |
| Start Page: | 16013 |
| Language: | English |
| DOI: | 10.1038/mto.2016.13 |
| PROVIDER: | scopus |
| PMCID: | PMC4909096 |
| PUBMED: | 27347556 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 3 January 2017 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work