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Involvement of vascular endothelial growth factor and urokinase‐type plasminogen activator receptor in microvessel invasion in human colorectal cancers
Author(s) -
Nakata Shinji,
Ito Kenichi,
Fujimori Minoru,
Shingū Kiyoshi,
Kajikawa Shoji,
Adachi Wataru,
Matsuyama Ikuo,
Tsuchiya Shinichi,
Kuwano Michihiko,
Amano Jun
Publication year - 1998
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19980417)79:2<179::aid-ijc14>3.0.co;2-5
Subject(s) - plasminogen activator , angiogenesis , vascular endothelial growth factor , colorectal cancer , urokinase receptor , plasminogen activator inhibitor 1 , pathology , urokinase , immunohistochemistry , biology , cancer research , cancer , microvessel , medicine , endocrinology , vegf receptors
To evaluate the association among known angiogenic growth factors or factors related to the plasminogen activation system and clinicopathological factors in patients with colorectal cancer, we examined the expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), transforming growth factor‐α (TGF‐α), urokinase‐type plasminogen activator (u‐PA), u‐PA receptor (u‐PA‐R) and plasminogen activator inhibitor‐1 (PAI‐1) in clinical specimens of colorectal cancers by Northern blot analysis. In comparison with the expression of these angiogenesis‐related genes in 7 paired samples of colorectal cancers and the adjacent normal mucosa, VEGF mRNA level was significantly higher in the cancer tissues than in the adjacent normal mucosa ( p < 0.05). We analyzed expression of these genes in 44 cases of primary colorectal cancers. Among the 3 angiogenic growth factors we examined, VEGF mRNA expression was significantly higher in the cancer tissues with blood vessel invasion or with lymphatic vessel invasion than in those without, respectively ( p < 0.05). On the other hand, u‐PA‐R mRNA expression was significantly higher in the cancers with blood vessel invasion than in those without ( p < 0.05). In addition, there was a correlation between the expression levels of VEGF and u‐PA‐R mRNA in the cancer tissues we have examined. Using immunohistochemistry, strong staining of VEGF or u‐PA‐R was observed in the cancer cells invading the microvessels. Our findings suggest that malignant transformation might accompany the upregulation of VEGF expression in colorectal cancers and that VEGF and u‐PA‐R might contribute cooperatively to increase angiogenesis around the tumor as well as the metastasis via microvessels. Int. J. Cancer (Pred. Oncol.) 79:179–186, 1998.© 1998 Wiley‐Liss, Inc.