Host CD147 blockade by small interfering RNAs suppresses growth of human colon cancer xenografts.
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.
Laboratory for Cardiovascular Research, Center of Anatomy and Cell Biology, Medical University of Vienna, Waehringerstrasse 13, A-1090 Vienna, Austria.
Dietmar
D
Abraham
Karin
K
Zins
Mouldy
M
Sioud
Trevor
T
Lucas
Seyedhossein
S
Aharinejad
D016475:3T3 Cells; D000818:Animals; D051926:Basigin / Q000235:genetics*; D002455:Cell Division; D003110:Colonic Neoplasms / Q000473:pathology*; D018076:DNA, Complementary / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008264:Macrophages / Q000502:physiology; D051379:Mice; D009368:Neoplasm Transplantation; D034741:RNA, Small Interfering / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000502:physiology; D014162:Transfection; D014183:Transplantation, Heterologous
D018076:DNA, Complementary; D034741:RNA, Small Interfering; D051926:Basigin