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Oncolytic Activity of a Recombinant Measles Virus, Blind to Signaling Lymphocyte Activation Molecule, Against Colorectal Cancer Cells.

Amagai Y, Fujiyuki T, Yoneda M, Shoji K, Furukawa Y, Sato H, Kai C - Sci Rep (2016)

Bottom Line: Oncolytic virotherapy is a distinctive antitumor therapy based on the cancer-cell-specific infectivity and killing activity of viruses, which exert a considerable antitumor effect with only a few treatments.Tumour progression in xenograft models was also abrogated by the virus, and the infection of cancer cells in vivo by the virus was demonstrated with both flow cytometry and a histological analysis.Therefore, rMV-SLAMblind is considered a novel therapeutic agent for colorectal cancers, including those resistant to molecular-targeted therapies.

View Article: PubMed Central - PubMed

Affiliation: Laboratory Animal Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.

ABSTRACT
Oncolytic virotherapy is a distinctive antitumor therapy based on the cancer-cell-specific infectivity and killing activity of viruses, which exert a considerable antitumor effect with only a few treatments. Because colorectal cancer cells often acquire resistance to the molecular-targeted therapies and alternative treatments are called for, in this study, we evaluated the oncolytic activity against colorectal cancer cells of a recombinant measles virus (rMV-SLAMblind), which is blind to signaling lymphocytic activation molecule (SLAM) and infects target cells via nectin-4/poliovirus receptor-related 4 protein. We examined 10 cell lines including 8 cell lines that were resistant to epidermal-growth-factor-receptor (EGFR) targeted therapy. rMV-SLAMblind infected and lysed the nectin-4-positive cell lines dependently on nectin-4 expression, in spite of mutation in EGFR cascade. Tumour progression in xenograft models was also abrogated by the virus, and the infection of cancer cells in vivo by the virus was demonstrated with both flow cytometry and a histological analysis. Therefore, rMV-SLAMblind is considered a novel therapeutic agent for colorectal cancers, including those resistant to molecular-targeted therapies.

No MeSH data available.


Related in: MedlinePlus

Infectivity and killing activity of rMV-EGFP-SLAMblind in colorectal cancer cells.(a) Representative fluorescence microscopy data. Cells were inoculated with rMV-EGFP-SLAMblind at MOI 2 and incubated for 72 h. Fluorescence microscopy was used to detect infection with rMV-EGFP-SLAMblind. Shown are representative data of three independent experiments. Original magnification, 20× objective lens. Bar, 100 μm. Changes in cell viability in nectin-4-positive (b) and nectin-4-negative (c) colorectal cancer cells. Cells were inoculated with rMV-EGFP-SLAMblind at MOI 2, and a WST assay was conducted on the indicated dpi. Each datum represents the mean ± SD of three independent experiments.
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f2: Infectivity and killing activity of rMV-EGFP-SLAMblind in colorectal cancer cells.(a) Representative fluorescence microscopy data. Cells were inoculated with rMV-EGFP-SLAMblind at MOI 2 and incubated for 72 h. Fluorescence microscopy was used to detect infection with rMV-EGFP-SLAMblind. Shown are representative data of three independent experiments. Original magnification, 20× objective lens. Bar, 100 μm. Changes in cell viability in nectin-4-positive (b) and nectin-4-negative (c) colorectal cancer cells. Cells were inoculated with rMV-EGFP-SLAMblind at MOI 2, and a WST assay was conducted on the indicated dpi. Each datum represents the mean ± SD of three independent experiments.

Mentions: To investigate the susceptibility of the colorectal cancer cells to rMV-SLAMblind, each cell line was inoculated with the virus at a multiplicity of infection (MOI) of 2 and examined with fluorescence microscopy at 3 days post-infection (dpi). To visualize viral infection, enhanced green fluorescent protein (EGFP)-expressing rMV-SLAMblind (rMV-EGFP-SLAMblind) was used, based on the previous observations that the insertion of EGFP does not affect the growth kinetics of rMVs2122. As shown in Fig. 2a, the replication of rMV-EGFP-SLAMblind was only observed in the nectin-4-positive cells. A water-soluble tetrazolium salt (WST) assay was performed to determine the killing activity of rMV-EGFP-SLAMblind in nectin-4-positive colorectal cancer cell lines. The inoculation of nectin-4-positive cells with rMV-EGFP-SLAMblind caused a time-dependent reduction in cell viability compared with that of the control (Fig. 2b). In contrast, the viabilities of nectin-4-negative cells were not altered after their inoculation with rMV-EGFP-SLAMblind (Fig. 2c).


Oncolytic Activity of a Recombinant Measles Virus, Blind to Signaling Lymphocyte Activation Molecule, Against Colorectal Cancer Cells.

Amagai Y, Fujiyuki T, Yoneda M, Shoji K, Furukawa Y, Sato H, Kai C - Sci Rep (2016)

Infectivity and killing activity of rMV-EGFP-SLAMblind in colorectal cancer cells.(a) Representative fluorescence microscopy data. Cells were inoculated with rMV-EGFP-SLAMblind at MOI 2 and incubated for 72 h. Fluorescence microscopy was used to detect infection with rMV-EGFP-SLAMblind. Shown are representative data of three independent experiments. Original magnification, 20× objective lens. Bar, 100 μm. Changes in cell viability in nectin-4-positive (b) and nectin-4-negative (c) colorectal cancer cells. Cells were inoculated with rMV-EGFP-SLAMblind at MOI 2, and a WST assay was conducted on the indicated dpi. Each datum represents the mean ± SD of three independent experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4835780&req=5

f2: Infectivity and killing activity of rMV-EGFP-SLAMblind in colorectal cancer cells.(a) Representative fluorescence microscopy data. Cells were inoculated with rMV-EGFP-SLAMblind at MOI 2 and incubated for 72 h. Fluorescence microscopy was used to detect infection with rMV-EGFP-SLAMblind. Shown are representative data of three independent experiments. Original magnification, 20× objective lens. Bar, 100 μm. Changes in cell viability in nectin-4-positive (b) and nectin-4-negative (c) colorectal cancer cells. Cells were inoculated with rMV-EGFP-SLAMblind at MOI 2, and a WST assay was conducted on the indicated dpi. Each datum represents the mean ± SD of three independent experiments.
Mentions: To investigate the susceptibility of the colorectal cancer cells to rMV-SLAMblind, each cell line was inoculated with the virus at a multiplicity of infection (MOI) of 2 and examined with fluorescence microscopy at 3 days post-infection (dpi). To visualize viral infection, enhanced green fluorescent protein (EGFP)-expressing rMV-SLAMblind (rMV-EGFP-SLAMblind) was used, based on the previous observations that the insertion of EGFP does not affect the growth kinetics of rMVs2122. As shown in Fig. 2a, the replication of rMV-EGFP-SLAMblind was only observed in the nectin-4-positive cells. A water-soluble tetrazolium salt (WST) assay was performed to determine the killing activity of rMV-EGFP-SLAMblind in nectin-4-positive colorectal cancer cell lines. The inoculation of nectin-4-positive cells with rMV-EGFP-SLAMblind caused a time-dependent reduction in cell viability compared with that of the control (Fig. 2b). In contrast, the viabilities of nectin-4-negative cells were not altered after their inoculation with rMV-EGFP-SLAMblind (Fig. 2c).

Bottom Line: Oncolytic virotherapy is a distinctive antitumor therapy based on the cancer-cell-specific infectivity and killing activity of viruses, which exert a considerable antitumor effect with only a few treatments.Tumour progression in xenograft models was also abrogated by the virus, and the infection of cancer cells in vivo by the virus was demonstrated with both flow cytometry and a histological analysis.Therefore, rMV-SLAMblind is considered a novel therapeutic agent for colorectal cancers, including those resistant to molecular-targeted therapies.

View Article: PubMed Central - PubMed

Affiliation: Laboratory Animal Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.

ABSTRACT
Oncolytic virotherapy is a distinctive antitumor therapy based on the cancer-cell-specific infectivity and killing activity of viruses, which exert a considerable antitumor effect with only a few treatments. Because colorectal cancer cells often acquire resistance to the molecular-targeted therapies and alternative treatments are called for, in this study, we evaluated the oncolytic activity against colorectal cancer cells of a recombinant measles virus (rMV-SLAMblind), which is blind to signaling lymphocytic activation molecule (SLAM) and infects target cells via nectin-4/poliovirus receptor-related 4 protein. We examined 10 cell lines including 8 cell lines that were resistant to epidermal-growth-factor-receptor (EGFR) targeted therapy. rMV-SLAMblind infected and lysed the nectin-4-positive cell lines dependently on nectin-4 expression, in spite of mutation in EGFR cascade. Tumour progression in xenograft models was also abrogated by the virus, and the infection of cancer cells in vivo by the virus was demonstrated with both flow cytometry and a histological analysis. Therefore, rMV-SLAMblind is considered a novel therapeutic agent for colorectal cancers, including those resistant to molecular-targeted therapies.

No MeSH data available.


Related in: MedlinePlus