Abstract 5885: Sialyl Lewis X-P-selectin connection between ovarian tumor-mesothelium in early stage metastasis

Metastasis is one of the major challenges for the treatment of ovarian cancer. Unlike other solid tumors, ovarian cancer primarily disseminates within the peritoneal cavity. A crucial step in metastasis formation is the adhesion of ovarian cancer cells onto the peritoneal mesothelium under ascitic shear flow. However, the adhesion mechanisms engaged in this tumor-mesothelium interaction remain elusive due to a lack of physiologically relevant model to manipulate and investigate this dynamic process. In this study, using a 3D microfluidic platform, we found that the metastatic population of cancer stem cells (M-CSCs) exhibited slower rolling velocity and higher binding ability to the peritoneal mesothelium than non-metastatic (NM)-CSCs under flow condition. This adhesion cascade was mediated by P-selectin which expressed on the peritoneal mesothelium. The key carbohydrate determinant on M-CSCs was a glycoprotein, but not a glycolipid, with its recognition as sialyl-Lewis X (sLe^X) in a sialic acid- and fucose-dependent manner. Moreover, several glycosyltransferase genes including B4GALT4, ST3GAL3, ST3GAL4 and FUT-5 involved the synthesis of sLe^X were upregulated in M-CSCs. Knocking down FUT-5 significantly inhibited ovarian tumor cell adhesion on the mesothelium in vitro and reduced the metastatic potential in vivo. Taken together, our findings revealed that a distinct sLe^X-P-selectin axis of ovarian tumor-mesothelium interaction in early metastasis and may offer the possibility of new therapeutic targets. (This work is supported by RGC grant 17122014) © 2017 American Association for Cancer Research.