Role of E-selectin in the modulation of metastatic phenotype

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA 3029 The selectins are a family of intercellular adhesion molecules with three members: E-, P- and L-selectin. E-selectin (ELAM-1, CD62E) is a type Ia transmembrane protein containing lectin-like and endothelial growth factor-like domains, followed by short cysteine-rich repeats. Absent in resting epithelium, E-selectin is rapidly expressed in the vascular lining during inflammation. Indeed, activation of endothelial cells by proinflammatory cytokines results in the cell surface appearance of E-selectin, facilitating leukocyte rolling and extravasation through activated endothelium. During a screening of gene expression in several human colon cancer cell lines we surprisingly identified E-selectin, as a molecule that was modulated in response to TNF-α. The up-regulation of E-selectin was also confirmed at the protein level with a mAb against human E-selectin. In order to better understand the role of E-selectin in the expression of tumor phenotype, we transfected T84 human colon cancer cells with the full length E-selectin cDNA and cDNA coding for the E-selectin shedded domain. We selected clones with a variable expression of the proteins and tested them for their ability to form aggregates, migrate, establish colonies in soft agar as well as to adhere to extracellular matrix substrates. The results we obtained strongly support the hypothesis that E-selectin plays an active role in metastatic cascade not only determining the extravasation site for tumor cells but also modulating growth rate and survival. Acknowledgments This work was supported by Italian Association for Cancer Research (AIRC)