Effect of all trans retinoic acid on lysosomal α-d-mannosidase activity in Hl-60 cell: correlation with Hl-60 cells differentiation

Abstract

Human promyelocytic leukemia HL-60 cells represent an in vitro model of acute promyelocytic leukemia (APL), and are inducible to terminally differentiate into morphologically mature granulocytes by incubation with all trans retinoic acid (ATRA). Lysosomal glycohydrolases are involved in the changes of the membrane surface proteins' glycosylation, linked to the metastatic progression potential of neoplastic cells. In particular, it has been demonstrated that the Asn-linked glucidic residues were directly responsible for the metastatic potential, and it is known that the glycohydrolase alpha-D-mannosidase specifically hydrolyze the Asn-linked oligosaccharides. In this report, we present an in vitro study on the ATRA effects on lysosomal glycohydrolases expression and the eventual relationship with the retinoic acid-induced differentiation of HL-60 cells. We have investigated two highly expressed lysosomal glycohydrolases, namely beta-D-hexosaminidase and alpha-D-mannosidase, and showed that they were differently affected by ATRA differentiating action. In particular, due to the specific action on Asn-linked oligosaccharides, we tested alpha-D: -mannosidase enzymatic activity and observed that it was dramatically decreased after ATRA incubation, indicating a relationship with the differentiation state of the cells. These observations may directly be linked with the loss of metastatic progession of differentiated HL-60.