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Blockade of host CD147 by small interfering RNAs suppresses growth of human colon cancer xenografts
Author(s) -
Abraham Dietmar,
Zins Karin,
Sioud Mouldy,
Lucas Trevor,
Aharinejad Seyedhossein
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.321.10
Subject(s) - basigin , stromal cell , cancer research , angiogenesis , cancer cell , colorectal cancer , cancer , cell growth , in vivo , cell , extracellular matrix , matrix metalloproteinase , chemistry , microbiology and biotechnology , biology , biochemistry , genetics
Tumor cells stimulate matrix metalloproteinase (MMP) production by stromal cells through cell–cell interactions mediated by adhesion molecules such as the extracellular MMP inducer (human CD147/EMMPRIN, mouse basigin). This study investigated whether tumor‐stromal cell interactions mediated by CD147 promote colon cancer growth by utilizing small interfering (si)RNAs directed against EMMPRIN or basigin in co‐cultures of cancer cells with macrophages and fibroblasts and human SW620 colon cancer xenografts in immune deficient mice. Blocking host basigin but not cancer cell‐derived EMMPRIN expression suppressed tumor growth in colon cancer xenografts illustrating the complex role of CD147 in tumor growth. Experiments in vitro showed CD147 mediated SW620‐stromal cell interactions led to increased MMP‐2 expression in fibroblasts but not macrophages. Expression of host vascular endothelial growth factor‐A in both fibroblasts and macrophages was independent of CD147 in vitro and in vivo . However, 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 regulating colon cancer growth and may lead to the development of novel siRNA‐based therapeutic strategies to treat patients with colon cancer.