Session Speaker

Effect of One Low Molecular Weight Polysaccharide (LMW-ABP) from Agaricus Blazei on Inhibiting Sialyl Lewis X/E-selectin-Mediated Metastatic Potential in HT-29 Cells and Its Mechanism
Jicheng Liu, Yongxu Sun
China

To the best of our knowledge, the metastatic spread of tumor cells is responsible for the majority of cancer patients' recurrence and deaths. Suppressing, the metastasizing capacity of cancer cells has been drawn more attentions by many research groups in realm of tumor therapy research. This research shows that adhesion of circulating tumor cells to vascular endothelium plays a crucial role in metastasis formation. This adhesion was mainly interacted by E-selectin expressed in activated endothelial cells and its ligand, sialyl Lewis X (sLex), expressed on the surface of tumor cells. In our previous investigation, one low molecular weight polysaccharide (LMW-ABP) of 4.8×104 Da was identified from the fruiting bodies of Agaricus blazei which possesses very potent anti-tumor and anti-metastasis activities. So in order to further investigate its molecular mechanisms of anti-metastasis. We choose E-selectin and its ligand, sLex, as the research target. Flow cytometry, real time-reverse transcription polymerase chain reaction (RT-PCR) and other techniques are used in this study to investigate whether LMW-ABP can inhibit neoplasm metastasis initiated by the adhesion of HT-29 cells to human umbilical vein endothelial cells (HUVECs) throuth suppressing the expression of FucT-VII in vitro.

First, cDNA of human FucT-VII is successfully cloned and inserted into pIRS2-EGFP, eukaryote-expression vector, and FucT-VII RNA interence system is also successfully constructed. Second, different concentrations of LMW-ABP (5, 10, and 20 mg/L) could effectively dose-dependently inhibit adhesion of HT-29 cells to HUVECs in static conditions, as well as down-regulating the expression of both α 1-3 fucosyltransferase-VII (FucT-VII) and sLex in transcription or translation level, respectively. These results suggest that LMW-ABP could suppress the metastasizing capacity of cancer cells through interfering with the interaction between E-selectin and sLex. Thus based on these findings, LMW-ABP is expected to be having enormou s potential for use in treatment for neoplasm metastasis.