The role of angiogenesis in the tumor growth of Syrian hamster pancreatic cancer cell line HPD-NR.
OBJECTIVE
New therapeutic approach is required for pancreatic cancer, one of the most intractable malignancies. The role of angiogenesis in the tumor growth of a Syrian hamster pancreatic cancer cell line HPD-NR, which closely resembles its human counterpart, was investigated.


METHODS
Angiogenic activity was measured as stimulation of growth of human umbilical vein endothelial cells (HUVEC), and angiogenic factors produced by HPD-NR cells were identified by reverse-transcription polymerase chain reaction and Northern blot analysis. Then in vitro and in vivo antitumor effects of a potent angiogenesis inhibitor, O-(chloroacetylcarbamoyl)fumagillol (AGM-1470), were examined.


RESULTS
The conditioned medium of HPD-NR cells stimulated the growth of HUVEC, and four hamster angiogenic factors were detected with an overexpression of transforming growth factor alpha and vascular endothelial growth factor messenger RNAs. AGM-1470 specifically inhibited the growth of HUVEC and that of HPD-NR tumors in vivo with decreased vascularity of the tumors but not the growth of HPD-NR cells in vitro.


CONCLUSIONS
The results suggest that angiogenesis plays an important role in tumor growth of HPD-NR cells and can be a new target of medical therapy for pancreatic cancer.
Egawa
S
S
Growth Factor Division, National Cancer Center Research Institute, Tokyo, Japan.
Tsutsumi
M
M
Konishi
Y
Y
Kobari
M
M
Matsuno
S
S
Nagasaki
K
K
Futami
H
H
Yamaguchi
K
K
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D001483:Base Sequence; D015152:Blotting, Northern; D018270:Carcinoma, Ductal, Breast / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D006224:Cricetinae; D003510:Cyclohexanes; D016228:Endothelial Growth Factors / Q000235:genetics; D008222:Lymphokines / Q000235:genetics; D008297:Male; D008647:Mesocricetus; D008969:Molecular Sequence Data; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D010190:Pancreatic Neoplasms / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D012717:Sesquiterpenes / Q000494:pharmacology; D016211:Transforming Growth Factor alpha / Q000235:genetics; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000903:Antibiotics, Antineoplastic; D003510:Cyclohexanes; D016228:Endothelial Growth Factors; D008222:Lymphokines; D012333:RNA, Messenger; D012717:Sesquiterpenes; D016211:Transforming Growth Factor alpha; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000077609:O-(Chloroacetylcarbamoyl)fumagillol