Transcriptional regulation of expression of carbohydrate ligands for cell adhesion molecules in the selectin family

Abstract

Cell adhesion mediated by selectins and their carbohydrate ligands is involved in the adhesion of cancer cells to endothelial cells during the course of hematogenous metastasis of cancer. In patients with leukemia, this adhesion is involved in the extravascular infiltration of leukemic cells. Extravasation and tissue infiltration of malignant cells in patients with adult T-cell leukemia is mediated by the interaction of selectins and their carbohydrate ligand sialyl Lewis X, which is strongly and constitutively expressed on the leukemic cells. Constitutive expression of Lewis X in these cells is due to the transcriptional activation of Fuc-T VII, the rate-limiting enzyme in the sialyl Lewis X synthesis, induced by the Tax protein encoded by the human T-cell leukemia virus-1, the etiological virus for this leukemia. This transactivation is in clear contrast to the regulation of typical CRE-element found in various cellular genes in that it is independent of phosphorylation-dependent regulation. This must be the reason for the strong and constitutive expression of sialyl Lewis X, which exacerbates the tissue infiltration of leukemic cells. This is a good example corroborating the proposition that the abnormal expression of carbohydrate determinant at the surface of malignant cells is intimately associated with the genetic mechanism of malignant transformation of cells.