Oncolytic viruses targeted, killed pancreatic cancer stem cells
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Digestive Disease Week 2011
CHICAGO — Oncolytic viruses eliminated more than 95% of pancreatic adenoma stem cells less than a week after infection and decreased the migratory capacity of the cancer stem cells, according to results of study presented here Monday.
Janice Wong, MD, a surgical researcher with Memorial Sloan-Kettering Cancer Center, presented the results and said the viruses NV1066 and NDV-F3aa-GFP may represent a potential treatment for cancers that are resistant to chemotherapy and radiotherapy. Pancreatic cancer has very poor prognosis, and the disease is difficult to treat or detect in its early stages.
"Oncolytic viruses can effectively infect and express the [green fluorescent protein] transgene in pancreatic stem cell spheroids, causing cell death" Wong said. "These viruses may offer therapy to prevent future cancer recurrence and metastases."
Researchers began by isolating a stem cell population from the MiaPaca-2 pancreatic adenocarcinoma cell line according to cell surface markers CD133 and CXCR4 and cultured in serum-free media. The stem cell spheroids were then infected with NV1066, a third-generation herpesvirus, or NDV-F3aa-GFP, a Newcastle disease virus mutant. Both viruses carried the marker gene green fluorescent protein (GFP), so they could be tracked by fluorescent microscopy.
Wong said the virus infected stem cells within 24 hours, and viruses from both families each produced efficient infection and killing of cancer. At doses of 0.5 or 1 virus particles per cell, more than 95% of stem cells were dead by day 6.
By day 2, we see a significant amount of tumor cell death, Wong said. By day 4, particularly in the NDV virally infected cells, there was marked cell death. By day 6, in both virally infected groups, nearly all cells were dead.
Wong said cytotoxicity correlated in an increase in viral production. Additionally, infection shifted the stem cell population to a higher fraction in S phase. - by Jason Harris
For more information:
- Wong J. #695. Presented at: Digestive Disease Week 2011; May 7-10, 2011; Chicago.
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