Enhanced expression of thrombospondin-1 and hypovascularity in human cholangiocarcinoma.
Cholangiocarcinoma (CCC) is relatively hypovascular, in contrast to hepatocellular carcinoma (HCC), which is often highly vascular. We investigated if the diminished vascularity of CCC is related to altered expression of thrombospondin-1 (TSP-1), an antiangiogenic factor, and/or vascular endothelial growth factor (VEGF), a potent angiogenic factor, comparing the relationships with those of high- and low-vascular HCC. We also investigated the relationship between the mutation of the p53 gene and TSP-1 expression or VEGF expression. Northern blot analysis and immunohistochemical staining were performed on surgically resected human CCC and HCC. The ratios of TSP-1 mRNA level in cancer cells versus adjacent noncancerous cells (T/N ratios) were significantly higher in CCC (n = 11) than in HCC with high vascularity (n = 15). In contrast, T/N ratios of VEGF mRNA level in CCC (n = 11) were comparable with those in HCC with low vascularity (n = 5). In CCC, the cancer cells and fibroblasts were positively stained with anti-TSP-1 antibody. We observed that T/N ratios of VEGF mRNA level, but not those of the TSP-1 mRNA level, were significantly correlated with vascularity in HCC. The relative increase in TSP-1 and the relative decrease in VEGF in tumors compared with normal tissue may underlie the limited angiogenesis of CCC. The p53 gene did not affect the expression of TSP-1 in CCC or VEGF in HCC.
Kawahara
N
N
Department of Biochemistry, Kyushu University School of Medicine, Kyushu University, Fukuoka, Japan.
Ono
M
M
Taguchi
K
K
Okamoto
M
M
Shimada
M
M
Takenaka
K
K
Hayashi
K
K
Mosher
D F
DF
Sugimachi
K
K
Tsuneyoshi
M
M
Kuwano
M
M
D000328:Adult; D000368:Aged; D001650:Bile Duct Neoplasms / Q000098:blood supply* / Q000378:metabolism*; D001653:Bile Ducts, Intrahepatic; D001808:Blood Vessels / Q000473:pathology; D015152:Blotting, Northern; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000378:metabolism; D018281:Cholangiocarcinoma / Q000098:blood supply* / Q000378:metabolism*; D016228:Endothelial Growth Factors / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000098:blood supply / Q000378:metabolism; D008222:Lymphokines / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D019700:Thrombospondin 1 / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D019700:Thrombospondin 1; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors