352회 Syndecan-2 is a key mediator of tumorigenesis and metastasis in c…

352회

연사 :  오 억 수, 이화여자대학교 생명과학과

제목: Syndecan-2 is a key mediator of tumorigenesis and metastasis in colon cancer

Abstract

The syndecans, a major family of transmembrane cell surface heparan sulfate proteoglycans, regulate ECM-mediated signal transduction including cell adhesion and migration. While syndecan-1 and syndecan-4 are known to inhibit cell migration, several reports indicate that syndecan-2 may have the opposite effect as the gene is highly expressed in cells under migratory conditions. Consistently, the expression of syndecan-1 and 4 is decreased in several cancer cell lines, while that of syndecan-2 was increased in colon cancer cell lines compared with normal colon epithelial cell lines, consistent with their migratory characteristics. Syndecan-2 expression was critical for colon cancer cell adhesion and proliferation as well as other tumorigenic behaviors such as anchorage-independent growth and increased metastasis. Therefore, increased syndecan-2 expression appears to be crucial for colon cell carcinogenesis. Consistently, reduction of syndecan-2 expression in colon cancer cells using either antisense syndecan-2 cDNA transfection or treatment with the specific histone deacetylase inhibitor, trichostatin A, reverted transformed phenotypes of colon cancer cells into detransformed ones, decreased metastasis and reduced anchorage-independent cell growth with concomitant increased actin filament organization. Interestingly, however, not all colon cancer cell lines showed increased syndecan-2 expression. Syndecan-2 was not detected either at mRNA or at protein level in certain colon cancer cell lines like HT29 and caco-2 which are known to express a high level of Cox-2.  In addition, Cox-2 expression was not detected in virtually all colon cancer cell lines that express a high level of syndecan-2. However, overexpression of syndecan-2 did not affect Cox-2 expression, implying the existence of different regulatory mechanisms of syndecan-2. In addition to cox-2, there are several known pathways involved in tumorigenesis of colorectal cancer. Current state of knowledge of syndecan-2 mediated tumorigenesis and metastasis of colon cancer cells will be presented including interactions with several prominent regulatory signal pathways implicated in colon cancer development.