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Enhanced expression of thrombospondin‐1 and hypovascularity in human cholangiocarcinoma
Author(s) -
Kawahara Naoyuki,
Ono Mayumi,
Taguchi Kenichi,
Okamoto Masahiro,
Shimada Mitsuo,
Takenaka Kenji,
Hayashi Kenshi,
Mosher Dean F.,
Sugimachi Keizo,
Tsuneyoshi Masazumi,
Kuwano Michihiko
Publication year - 1998
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.510280610
Subject(s) - vascularity , thrombospondin 1 , angiogenesis , immunohistochemistry , hepatocellular carcinoma , vascular endothelial growth factor , thrombospondin , messenger rna , cancer research , pathology , biology , medicine , vegf receptors , gene , biochemistry , metalloproteinase , matrix metalloproteinase
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.