2002年1月
Cyclooxygenase 2-and prostaglandin E-2 receptor EP2-dependent angiogenesis in Apc(Delta 716) mouse intestinal polyps
CANCER RESEARCH
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- 巻
- 62
- 号
- 2
- 開始ページ
- 506
- 終了ページ
- 511
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- 出版者・発行元
- AMER ASSOC CANCER RESEARCH
To investigate angiogenesis during intestinal polyp development, we determined the microvessel density (MVD) in polyps of Apc knockout (Apc(Delta716)) mice, a model for human familial adenomatous polyposis. We scored MVD also in several compound mutants carrying Apc(Delta716), namely, mice with an additional mutation in Smad4. in which the polyps progress into invasive adenocarcinomas, mice with a cyclooxygenase COX-2 gene (Ptgs2) mutation, in which adenoma growth is suppressed; and mice with prostaglandin E-2 EP receptor gene mutations. In both simple Ap(Delta716) and compound Apc(Delta716) Smad4 mutants, MVD increased in a polyp size-dependent manner only in the polyps expanded beyond a threshold of about 1 mm in diameter. These results indicate that tumor angiogenesis is stimulated only after tumors grow to a certain size, and this angiogenic switch is common to both benign adenomas and malignant adenocarcinomas. in Apc(Delta716) polyposis attenuated by the COX-2 gene mutation, in contrast, MVD did not increase even in polyps larger than 1 mm. The same phenomenon was observed in the compound mutant mice with Apc(Delta716) and the EP2 receptor gene mutations, but not in other EP compound mutants. We also immunohistochemically studied COX-2 and angiogenic factors. vascular endothelial growth factor and basic fibroblast growth factor. Interestingly, expression of these proteins was also increased in polyps larger than 1 mm. These results suggest that, in both benign and malignant mouse intestinal tumors, stromal expression of COX-2 results in elevated prostaglandin E-2 levels that stimulate cell surface receptor EP2, followed by induction of vascular endothelial growth factor that causes tumor angiogenesis.
- リンク情報
- ID情報
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- ISSN : 0008-5472
- PubMed ID : 11809702
- Web of Science ID : WOS:000173488700030