Mechanism study of Doppel protein in human colorectal cancer

Abstract

Angiogenesis is a biological process that is essential not only for normal tissue growth and development but also for cancer growth and metastasis. Although anticancer agents that inhibit angiogenesis have been actively developed, there is a limit in that the target of these agents are commonly expressed in both normal tissues and cancers, so that the angiogenesis is inhibited without any distinction. Herein, this study targeted the colorectal cancer and identified the mechanism of protein 'Doppel,' which is expressed much more in tumor endothelial cells than normal endothelial cells.

Experimental results showed that Doppel antibody reduced phosphorylation of VEGFR-2 & FGFR-1, the two most essential receptors involved in angiogenesis and Doppel is located from 10 nm range with FGFR-1 on the cell membrane.

Furthermore, Doppel antibody also affected β-catenin and STAT 5a which are related to VEGF-A expression and sensitivity of chemotherapeutic agents to colorectal cancer. In animal models of colorectal cancer, Doppelantibody showed more than 50% anticancer effect. Taken together, Doppel is associated with both angiogenesis and chemotherapeutic sensitivity in colorectal cancer. This study is novel in that it is the first study of Doppel's role in colorectal cancer. The detailed mechanism which will be studied in future research would allow the colorectal cancer patients to use the Doppel antibodies as a way to overcome the limitations of cancer recurrence, resistance, and side effects associated with conventional anticancer agents.