Systemic shRNA mediated knock-down of S100A4 in colorectal cancer xenografted mice reduces metastasis formation
The metastasis-inducing protein S100A4 was found to be a prognostic indicator for the development of metachronous metastases. S100A4 expression levels correlate with the formation of human colorectal cancer metastases and shorter patients’ survival. Inhibition of S100A4 expression in patients might...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3478456/ https://www.ncbi.nlm.nih.gov/pubmed/22878175 |
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author | Dahlmann, Mathias Sack, Ulrike Herrmann, Pia Lemm, Margit Fichtner, Iduna Schlag, Peter M. Stein, Ulrike |
author_facet | Dahlmann, Mathias Sack, Ulrike Herrmann, Pia Lemm, Margit Fichtner, Iduna Schlag, Peter M. Stein, Ulrike |
author_sort | Dahlmann, Mathias |
collection | PubMed |
description | The metastasis-inducing protein S100A4 was found to be a prognostic indicator for the development of metachronous metastases. S100A4 expression levels correlate with the formation of human colorectal cancer metastases and shorter patients’ survival. Inhibition of S100A4 expression in patients might therefore result in decreased metastasis formation and prolonged survival. In the present study, we used shRNA expression plasmids to inhibit S100A4 expression in the colorectal cancer cell lines HCT116, SW620 and DLD-1. Cell lines with reduced S100A4 expression showed reduced cell migration and invasion in vitro. The knock-down of S100A4 expression also led to significantly diminished formation of liver metastases when intrasplenically transplanted in mice (P = 0.004). We then focused on the therapeutic potential of systemically applied shRNA expression plasmids acting on S100A4 via repeated hydrodynamics-based tail vein injection of plasmid DNA. Mice, intrasplenically transplanted with HCT116 cells and treated systemically with S100A4-shRNA plasmids, showed a decrease of S100A4 and MMP9 expression levels, resulting in significantly reduced liver metastases (P = 0.005). In summary, we show for the first time the intratumoral knock-down of S100A4 via systemic application of S100A4-shRNA plasmid DNA, which restricts metastasis formation in a xenografted mouse model of colorectal cancer. |
format | Online Article Text |
id | pubmed-3478456 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-34784562012-10-24 Systemic shRNA mediated knock-down of S100A4 in colorectal cancer xenografted mice reduces metastasis formation Dahlmann, Mathias Sack, Ulrike Herrmann, Pia Lemm, Margit Fichtner, Iduna Schlag, Peter M. Stein, Ulrike Oncotarget Research Papers The metastasis-inducing protein S100A4 was found to be a prognostic indicator for the development of metachronous metastases. S100A4 expression levels correlate with the formation of human colorectal cancer metastases and shorter patients’ survival. Inhibition of S100A4 expression in patients might therefore result in decreased metastasis formation and prolonged survival. In the present study, we used shRNA expression plasmids to inhibit S100A4 expression in the colorectal cancer cell lines HCT116, SW620 and DLD-1. Cell lines with reduced S100A4 expression showed reduced cell migration and invasion in vitro. The knock-down of S100A4 expression also led to significantly diminished formation of liver metastases when intrasplenically transplanted in mice (P = 0.004). We then focused on the therapeutic potential of systemically applied shRNA expression plasmids acting on S100A4 via repeated hydrodynamics-based tail vein injection of plasmid DNA. Mice, intrasplenically transplanted with HCT116 cells and treated systemically with S100A4-shRNA plasmids, showed a decrease of S100A4 and MMP9 expression levels, resulting in significantly reduced liver metastases (P = 0.005). In summary, we show for the first time the intratumoral knock-down of S100A4 via systemic application of S100A4-shRNA plasmid DNA, which restricts metastasis formation in a xenografted mouse model of colorectal cancer. Impact Journals LLC 2012-08-07 /pmc/articles/PMC3478456/ /pubmed/22878175 Text en Copyright: © 2012 Dahlmann et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited |
spellingShingle | Research Papers Dahlmann, Mathias Sack, Ulrike Herrmann, Pia Lemm, Margit Fichtner, Iduna Schlag, Peter M. Stein, Ulrike Systemic shRNA mediated knock-down of S100A4 in colorectal cancer xenografted mice reduces metastasis formation |
title | Systemic shRNA mediated knock-down of S100A4 in colorectal cancer xenografted mice reduces metastasis formation |
title_full | Systemic shRNA mediated knock-down of S100A4 in colorectal cancer xenografted mice reduces metastasis formation |
title_fullStr | Systemic shRNA mediated knock-down of S100A4 in colorectal cancer xenografted mice reduces metastasis formation |
title_full_unstemmed | Systemic shRNA mediated knock-down of S100A4 in colorectal cancer xenografted mice reduces metastasis formation |
title_short | Systemic shRNA mediated knock-down of S100A4 in colorectal cancer xenografted mice reduces metastasis formation |
title_sort | systemic shrna mediated knock-down of s100a4 in colorectal cancer xenografted mice reduces metastasis formation |
topic | Research Papers |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3478456/ https://www.ncbi.nlm.nih.gov/pubmed/22878175 |
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