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Susceptibility of colorectal cancer cells to Sindbis virus infection
Chao Li1, Youling Gu, Dario Andrade
1Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73190, USA.
Abstract:
Sindbis virus (SIN), a member of the Togaviridae family, infects a broad range of cells and has been shown to be an effective anti-tumor agent. The infection efficiency of the virus, however, varies greatly among target cells. In this report, we compared the ability of SIN to infect colorectal cancer cells and cells of other cancer origin. While tumor cells from breast, leukemia, and prostate cancers were largely resistant to SIN infection, nine of the ten colorectal cancer cell lines tested were sensitive to SIN infection. Moreover, SIN susceptibility correlated with the metastatic potential of the colorectal cancer cells. Two highly aggressive and invasive cell lines, SW620 and COLO-320DM were the most sensitive to SIN infection. Similarly, SIN preferentially targeted metastatic tumor cells in a mouse xenograft model for colon cancer progression. The higher infection rate was not due to increased expression of the 67kD laminin receptor, a specific receptor for SIN infection, although viral attachment and entry were markedly enhanced in SW620 cells. These results suggest that SIN may employ a novel cell attachment/entry mechanism during infection, allowing selective targeting of colorectal cancer cells.
Insights
Sindbis virus (SIN) shows promise as an anti-tumor agent, selectively infecting colorectal cancer cells. This virus preferentially targets aggressive and metastatic cancer cells, suggesting a novel infection mechanism.
Area of Science:
- Virology
- Oncology
- Cancer Biology
Background:
- Sindbis virus (SIN), a Togaviridae family member, is an effective anti-tumor agent with variable infection efficiency across cell types.
- Understanding SIN's tropism is crucial for optimizing its oncolytic potential.
Purpose of the Study:
- To compare SIN infection efficiency in colorectal cancer cells versus other cancer types.
- To investigate the correlation between SIN susceptibility and colorectal cancer cell metastatic potential.
Main Methods:
- Infection assays were performed on ten colorectal cancer cell lines and cell lines from breast, leukemia, and prostate cancers.
- A mouse xenograft model was used to assess SIN targeting of metastatic colon cancer cells.
- Viral attachment and entry mechanisms were analyzed, including 67kD laminin receptor expression.
Main Results:
- Nine out of ten colorectal cancer cell lines were sensitive to SIN infection, while breast, leukemia, and prostate cancer cells were largely resistant.
- SIN susceptibility positively correlated with the metastatic potential of colorectal cancer cells, with SW620 and COLO-320DM showing highest sensitivity.
- SIN preferentially targeted metastatic cells in vivo, independent of 67kD laminin receptor expression, indicating enhanced viral attachment and entry.
Conclusions:
- Sindbis virus demonstrates selective tropism for colorectal cancer cells, particularly those with high metastatic potential.
- The virus may utilize a novel mechanism for cell attachment and entry, distinct from the 67kD laminin receptor.
- These findings support SIN's potential as a targeted oncolytic virotherapy for colorectal cancer.
