IMR Press / FBL / Volume 13 / Issue 14 / DOI: 10.2741/3100

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
Host CD147 blockade by small interfering RNAs suppresses growth of human colon cancer xenografts
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1 Laboratory for Cardiovascular Research, Center of Anatomy and Cell Biology, Medical University of Vienna, Waehringerstrasse 13, A-1090 Vienna, Austria
2 Department of Immunology, Molecular Medicine Group, The Norwegian Radium Hospital, Montebello, Oslo 0301, Norway
Academic Editor:Mouldy Sioud
Front. Biosci. (Landmark Ed) 2008, 13(14), 5571–5579; https://doi.org/10.2741/3100
Published: 1 May 2008
(This article belongs to the Special Issue RNA interference: from basic to medical applications)
Abstract

Tumor cells can stimulate matrix metalloproteinase (MMP) production by stromal cells through cell–cell interactions mediated by cell adhesion molecules such as extracellular matrix metalloproteinase inducer (human CD147/EMMPRIN, mouse CD147/Basigin). This study sought to characterize whether specific tumor-stromal cell interactions mediated by CD147 promote colon cancer growth by utilizing small interfering (si)RNAs directed against human CD147/EMMPRIN or mouse CD147/Basigin in co-cultures of cancer cells with macrophages and fibroblasts and established human SW620 colon cancer xenograft models in immune deficient mice. We show that blockade of host (mouse) CD147/Basigin expression, but not cancer cell-derived CD147/EMMPRIN, suppresses tumor growth in human colon cancer xenografts. Experiments in vitro indicated that colon cancer cell-stromal cell interactions mediated by CD147 lead to increased MMP-2 expression in fibroblasts but not macrophages. Furthermore, expression of host VEGF-A in both fibroblasts and macrophages is independent of CD147 in vitro and in vivo. Interestingly, inhibition of cancer cell-derived EMMPRIN leads to increased MMP-9 levels in vivo. Our findings provide new insights into CD147-mediated tumor-host interactions mediating colon cancer growth.

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