Expression of activated platelet-derived growth factor receptor in stromal cells of human colon carcinomas is associated with metastatic potential
Yasuhiko Kitadai
Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX
Search for more papers by this authorTakamitsu Sasaki
Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX
Search for more papers by this authorToshio Kuwai
Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX
Search for more papers by this authorToru Nakamura
Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX
Search for more papers by this authorCorazon D. Bucana
Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX
Search for more papers by this authorStanley R. Hamilton
Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX
Search for more papers by this authorCorresponding Author
Isaiah J. Fidler
Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX
Fax: +713-792-8747
Department of Cancer Biology, Unit 173, The University of Texas MD Anderson Cancer Center, P. O. Box 301429, Houston, TX 77230-1429, USA.Search for more papers by this authorYasuhiko Kitadai
Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX
Search for more papers by this authorTakamitsu Sasaki
Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX
Search for more papers by this authorToshio Kuwai
Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX
Search for more papers by this authorToru Nakamura
Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX
Search for more papers by this authorCorazon D. Bucana
Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX
Search for more papers by this authorStanley R. Hamilton
Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX
Search for more papers by this authorCorresponding Author
Isaiah J. Fidler
Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX
Fax: +713-792-8747
Department of Cancer Biology, Unit 173, The University of Texas MD Anderson Cancer Center, P. O. Box 301429, Houston, TX 77230-1429, USA.Search for more papers by this authorAbstract
Platelet-derived growth factor receptor (PDGF-R) expression has been reported in a variety of cancers, including colorectal, breast, lung, ovarian and pancreatic cancers, but the role of PDGF-R expression in the development and progression of colon carcinoma has not yet been elucidated. The purpose of this study was to examine the expression of PDGF and PDGF-R in human colon carcinomas. The expression of PDGF, PDGF-R and phosphorylated PDGF-R (p-PDGF-R) was examined by immunofluorescence in 12 surgical specimens of colon carcinoma and in human colon carcinoma cells growing in the subcutis (ectopic site) and the cecal wall (orthotopic site) of nude mice. In most surgical specimens, tumor cells expressed PDGF-A and -B subunits, without corresponding levels of PDGF-Rα and PDGF-Rβ. PDGF-Rβ was predominantly expressed by tumor-associated stromal cells and pericytes of tumor vasculature. The expression of PDGF-Rβ in the stroma was associated with advanced stage disease. Under culture conditions, human colon carcinoma cell lines expressed PDGF-A and -B, but not PDGF-R. In orthotopic tumors, the KM12 cells (Duke's stage B) expressed PDGF-A and -B, but PDGF-Rβ was expressed only by stromal cells and pericytes in the tumor vasculature. This expression of PDGF-Rβ by stromal cells and pericytes was higher in tumors growing at the orthotopic site than in those at the ectopic site. The expression of PDGF-Rβ in the stroma was higher in highly metastatic KM12SM tumors than in low metastatic KM12C tumors. In conclusion, the expression of PDGF-Rβ in stromal cells is influenced by the organ-specific microenvironment and is associated with metastatic potential. © 2006 Wiley-Liss, Inc.
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