Overexpression of lymphangiogenic growth factor VEGF-C in human pancreatic cancer.
Vascular endothelial growth factor C (VEGF-C) is a lymphangiogenic polypeptide that has been implicated in cancer growth. In this study, we characterized VEGF-C expression in cultured human pancreatic cancer cell lines and determined whether the presence of VEGF-C in human pancreatic cancers is associated with clinicopathologic characteristics. VEGF-C mRNA transcripts were present in all five tested cell lines (Capan-1, MIA-PaCa-2, PANC-1, COLO-357, and T3M4). Immunoblotting with a highly specific anti-VEGF-C antibody revealed the presence of VEGF-C protein in all the cell lines. Northern blot analysis of total RNA revealed an approximately 2.2-fold increase in VEGF-C mRNA transcript in the cancer samples compared with the normal pancreas. Immunohistochemical analysis confirmed the expression of VEGF-C and its receptor flt-4 in the cancer cells within the tumor mass. Immunohistochemical analysis of 51 pancreatic cancer tissues revealed the presence of strong VEGF-C immunoreactivity in the cancer cells in 80.4% of the cancer tissues. The presence of VEGF-C in these cells was associated with increased lymphatic vessels invasion and lymph node metastasis, but not with decreased patient survival. These findings indicate that VEGF-C and its receptor are commonly overexpressed in human pancreatic cancers and that this factor may contribute to the lymphangiogenic process and metastasis in this disorder.
Tang
R F
RF
First Department of Surgery, Yamanashi Medical University, Nakakoma, Japan.
Itakura
J
J
Aikawa
T
T
Matsuda
K
K
Fujii
H
H
Korc
M
M
Matsumoto
Y
Y
D015152:Blotting, Northern; D016228:Endothelial Growth Factors / Q000235:genetics*; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D009361:Neoplasm Invasiveness; D010179:Pancreas / Q000737:chemistry; D010190:Pancreatic Neoplasms / Q000737:chemistry* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis*; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis; D017978:Receptors, Growth Factor / Q000032:analysis; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D042582:Vascular Endothelial Growth Factor C; D040321:Vascular Endothelial Growth Factor Receptor-3
D016228:Endothelial Growth Factors; D012333:RNA, Messenger; D017978:Receptors, Growth Factor; D042582:Vascular Endothelial Growth Factor C; D020794:Receptor Protein-Tyrosine Kinases; D040321:Vascular Endothelial Growth Factor Receptor-3