Colon Cancer and Midkine

Abstract

Midkine, a heparin-binding growth factor, promotes the growth, survival, and migration of various cell populations, and it is over-expressed in many malignant human tumors. Midkine expression is generally increased in colon carcinomas compared to normal colon tissue. Additionally, colon adenomas with medium-to severe-dysplasia exhibit increased midkine expression. Therefore, midkine is expressed during the early stages of colon carcinogenesis and is likely to be involved in the oncogenic process, presumably by promoting tumor cell growth and survival. In the advanced tumor stages, midkine is expected to contribute to tumor progression by promoting tumor angiogenesis. A truncated form of midkine mRNA, which lacks the sequence encoding the N-terminal domain, is expressed in colon cancers in a cancer-specific manner. Detection of this sequence might help to detect micro metastases. Furthermore, the truncated midkine mRNA appears to contribute to colon carcinogenesis because a genetic variant favoring its formation is more frequently found in patients with colon carcinoma compared to unaffected controls. Finally, midkine inhibitors are expected to be valuable in colon cancer treatment; antisense oligo-DNA has been proven to suppress cancer growth in experimental systems. © 2012 Springer Science+Business Media Dordrecht. All rights reserved.