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

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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.