Carcinoembryonales Antigen (CEA) induziert metastatisches Wachstum von Colonkarzinom Zellen vermutlich aufgrund anti-apoptotischer Eigenschaften
Carcinoembryonic antigen (CEA) is a membrane anchored 180 kDa glycoprotein which is widely used as a serum tumor marker in colon cancer patients. High CEA levels indicate metastatic relapse after an apparently curative surgical Intervention. The biological function of CEA is barely understood. The aim of this study was to analyze the role of CEA in colon cancer progression.
To study CEA’s biological function, we used human HT29 colon cancer cells expressing CEA targeted ribozymes under control of a tet-off promoter. This model allowed us to regulate endogeneous CEA levels by 50% and, thus, to analyze the CEA-related phenotype (addition of tetracycline inhibits ribozyme expression and, subsequently, restores CEA levels).
An aggregate formation assay confirmed an adhesive function of CEA because ribozyme expression (low CEA levels) reduced the aggregate formation rate by 70%. While CEA did not affect the proliferation rate we observed a significantly increased apoptotic rate in CEA diminished cells when treated with various inducers of apoptosis such as 5-Fluorouracil, gamma-interferon, UV-light and confluent growth. The impact of CEA’s protective function was also reflected by a 30 – 50% increase in colony formation and metastatic rate in vivo. Western blot analysis indicated that CEA binds to a tyrosine phosphorylated 80 kDa protein forming a ~ 250 kDa complex with this protein and, thus, suggests this molecule as a signaling partner for CEA.
Our studies indicate that CEA participates in signal transduction and promotes metastatic growth of colon cancer cells assumingly by protecting tumor cells from undergoing apoptosis.
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