Abstract
Stromal angiogenesis is an important factor for progression of malignant neoplasms. We used hammerhead ribozymes against vascular endothelial growth factor (VEGF) gene transcripts to down-regulate cell-associated VEGF189 isoform function in the pancreatic cancer cell line MIA PaCa2. MIA PaCa2 transfected with anti-VEGF189 ribozyme did not show any alteration of growth rate under tissue culture. When the transformants were subcutaneously transplanted, tumour volume of the ribozyme-transfected MIA PaCa2 xenografts was significantly smaller (P<0.01). No metastasis of MIA PaCa2 transfected with anti-VEGF189 was apparent, while disabled ribozyme-transfected MIA PaCa2 showed significant liver metastasis (P<0.05). These results suggested that VEGF189 plays an important role in growth and metastatic potential through alteration of angiogenic balance in cancer.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Endothelial Growth Factors / antagonists & inhibitors
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Endothelial Growth Factors / genetics*
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Humans
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Intercellular Signaling Peptides and Proteins / genetics*
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Liver Neoplasms / prevention & control*
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Liver Neoplasms / secondary*
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Lymphokines / antagonists & inhibitors
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Lymphokines / genetics*
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Mice
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Neoplasm Transplantation
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Pancreatic Neoplasms / blood supply
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Pancreatic Neoplasms / drug therapy*
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Pancreatic Neoplasms / pathology
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Protein Isoforms
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RNA, Catalytic / therapeutic use*
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RNA, Messenger / metabolism
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Tissue Plasminogen Activator / biosynthesis
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Transplantation, Heterologous
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Tumor Cells, Cultured
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factors
Substances
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Endothelial Growth Factors
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Intercellular Signaling Peptides and Proteins
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Lymphokines
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Protein Isoforms
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RNA, Catalytic
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RNA, Messenger
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VEGFA protein, human
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factors
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Tissue Plasminogen Activator