Die Rolle von CD97 in der Entstehung, Invasion und Metastasierung kolorektaler Karzinome (CD97 - elucidating the role in colorectal carcinoma development, invasion and metastasis)

CD97在结直肠癌发生、侵袭和转移中的作用（CD97 - 阐明在结直肠癌发生、侵袭和转移中的作用）

• 批准号: 5401724
• 负责人: Professorin Dr. Gabriela Aust
• 金额: --
• 依托单位: Forschungslaboratorien der Chirurgischen Kliniken I und II
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2003
• 资助国家: 德国
• 起止时间: 2002-12-31 至 2006-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5401724?language=en
• 关键词: Die; Rolle; von; CD97; der

The EGF-TM7 receptor CD97 has been described originally by us as a leukocyte activation marker. We recently showed expression of CD97 outside the haematopoietic system on anaplastic thyroid and colorectal carcinomas but not in the corresponding normal tissues. The presence of highly CD97-positive scattered tumor cells at the invasion front of colorectal carcinomas correlates with the presence of the CD97 ligand, CD55, in the tumor microenvironment. Clinically, expression of CD97 coincides with high tumor stage and lymph vessel invasion. Thus, our data suggest the involvement of CD97 in colorectal cancer progression. Whithin this research collaboration, laboratories with a specific interest in the molecular and tumor biology of CD97 will investigate the role of this molecule in development, invasive growth and metastasis of colorectal carcinomas. Specifically, the following problems will be addressed: A) The process of CD97 upregulation on tumor cells will be studied. We will investigate whether CD97 is a Tcf-4 target gene regulated through the Wnt pathway. B) The distribution of CD97 on scattered tumor cells at the invasion front and solid tumor formations will be compared between primary colorectal carcinomas, metastases and recidives and related to characteristics of the tumor microenvironment. The process of scattered tumor-cell formation will be mimicked in vitro by modulation of the tumor environment. C) The role of CD97 in tumorigenesis will be studied in vivo. We will analyze the effect of CD97 expression on the outgrowth of established colorectal mouse tumors by comparing wild-type and CD97 knock-out mice. In transgenic mice, the consequences of enterocyte-specific CD97 expression on development, metastasis and invasion of colorectal carcinomas will be investigated. D) The molecular basis for the observed differences in the expression /accessibility of CD97EGF and CD97stalk epitopes will be clarified. Work carried out during this project will increase our knowledge about CD97 as a marker for tumor diagnosis and prognosis as well as a potential target for novel therapeutic approaches.

EGF-TM7受体CD97最初被我们描述为一种白细胞激活标志。我们最近发现CD97在间变性甲状腺癌和结直肠癌的造血系统外表达，但在相应的正常组织中不表达。结直肠癌侵袭前沿CD97高阳性散在肿瘤细胞的存在与肿瘤微环境中CD97配体CD55的存在有关。临床上，CD97的表达与肿瘤的高分期和淋巴管侵犯相一致。因此，我们的数据提示CD97参与了结直肠癌的进展。在这项研究合作中，对CD97的分子和肿瘤生物学特别感兴趣的实验室将研究该分子在结直肠癌的发展、侵袭生长和转移中的作用。具体地说，将解决以下问题：a)研究CD97上调肿瘤细胞的过程。我们将研究CD97是否是通过Wnt途径调节的Tcf-4靶基因。2)比较CD97在原发、转移和复发结直肠癌侵袭前沿和实体瘤细胞上的分布，并与肿瘤微环境的特点进行比较。通过调节肿瘤环境，可以在体外模拟分散的肿瘤细胞的形成过程。C)CD97在肿瘤发生中的作用将在体内进行研究。我们将通过比较野生型和CD97基因敲除小鼠来分析CD97表达对已建立的结直肠癌小鼠生长的影响。在转基因小鼠中，将研究肠道细胞特异性CD97表达对结直肠癌发生、转移和侵袭的影响。D)CD97EGF和CD97istk表位表达/可及性差异的分子基础将被阐明。在该项目期间开展的工作将增加我们对CD97作为肿瘤诊断和预后标记物以及新治疗方法的潜在靶点的了解。