Modulation of Tumor Angiogenesis by CEACAM1 in a Mouse Model for Mammary Carcinogenesis (WAP-T Mice)

CEACAM1 在乳腺癌发生小鼠模型（WAP-T 小鼠）中对肿瘤血管生成的调节

• 批准号: 22012230
• 负责人: Professor Dr. Wolfgang Deppert
• 金额: --
• 依托单位: Leibniz-Institut für Virologie (LIV)
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2006
• 资助国家: 德国
• 起止时间: 2005-12-31 至 2009-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/22012230?language=en
• 关键词: Modulation; Tumor; Angiogenesis; CEACAM1; Mouse

Tumor development and progression in WAP-T mice, modelling human mammary carcinogenesis, is characterized by an initial phase of enhanced angiogenesis in low grade tumors (G0 and G1 grade), followed by insufficient angiogenesis in moderately and poorly differentiated adenocarcinoma (G2 and G3 grade), thereby leading to tumor necrosis in the central mass of the tumor. However, angiogenesis increases again in undifferentiated and anaplastic tumors (G4 grade) ( angiogenic switch ). The WAP-T mouse system thus is extremely well suited to test the effects of modulators of angiogenesis on tumor progression and metastasis. We want to analyze the effects of the angiogenic factor CEACAM1 on tumor development and progression in WAP-T mice, WAP-T mice will be crossed with mice overexpressing CEACAM1 in endothelial cells (CEACAM1endo+ mice), or with mice in which functional CEACAM1 expression in endothelial cells is blocked by overexpression of a dominant-negative CEACAM1 (CEACAM1endo+ mice), respectively. Comparative phenotypic and molecular analyses of WAP-T and WAP-T x CEACAM1 mice will elucidate the influence of endothelial CEACAM1 on tumor vascularization and stroma formation at different stages of tumor development and progression, and reveal the cross-talk between CEACAM1 and other angiogenic factors, Using WAP-T x CEACAM1K0 mice, we will analyze the possible mutual relationship between endothelial and epithelial CEACAM1 expression during tumor formation and progression. An important general goal of our planned investigations is to define molecular parameters influencing the angiogenic switch in high-grade WAP-T tumors, as this switch might relate to the metastatic potential of these tumors.

WAP-T小鼠中的肿瘤发展和进展（模拟人类乳腺癌发生）的特征在于低级别肿瘤（G 0和G1级）中血管生成增强的初始阶段，随后是中等分化和低分化腺癌（G2和G3级）中血管生成不足，从而导致肿瘤中心块的肿瘤坏死。然而，在未分化和间变性肿瘤（G4级）中血管生成再次增加（血管生成转换）。因此，WAP-T小鼠系统非常适合于测试血管生成调节剂对肿瘤进展和转移的影响。我们想分析血管生成因子CEACAM 1对WAP-T小鼠肿瘤发生和进展的影响，WAP-T小鼠将分别与内皮细胞中过表达CEACAM 1的小鼠（CEACAM 1 endo+小鼠）或与内皮细胞中功能性CEACAM 1表达被显性阴性CEACAM 1过表达阻断的小鼠（CEACAM 1 endo+小鼠）杂交。WAP-T和WAP-T x CEACAM 1小鼠的比较表型和分子分析将阐明内皮CEACAM 1在肿瘤发展和进展的不同阶段对肿瘤血管形成和基质形成的影响，并揭示CEACAM 1与其他血管生成因子之间的相互作用。我们将分析肿瘤形成和发展过程中内皮细胞和上皮细胞CEACAM 1表达之间可能的相互关系。我们计划研究的一个重要总体目标是确定影响高级别WAP-T肿瘤血管生成转换的分子参数，因为这种转换可能与这些肿瘤的转移潜力有关。