Overexpression of lysosomal-type sialidase leads to suppression of metastasis associated with reversion of malignant phenotype in murine B16 melanomacells

Increased sialylation in cell surface glycoproteins is one characteristic f eature of cancer cells, particularly related to their metastatic potential and invasiveness. Expression of lysosomal-type sialidase, which plays a maj or role in hydrolysis of such sialo-glycoproteins, is therefore considered to have a great influence on malignant properties of cancer cells. To inves tigate whether the sialidase expression level is linked to the malignant ph enotype, we transfected B16-BL6 murine melanoma cells, a highly invasive an d metastatic line, with an expression vector harboring a rat lysosomal sial idase cDNA; then clones were isolated and examined for changes in biologica l character. Sialidase-overexpressing cells showed suppression of experimen tal pulmonary metastasis and tumor progression. The transfectants exhibited diminished cell growth, anchorage-independent growth and increased sensiti vity to apoptosis induced by suspension culture or serum depletion in vitro , but no significant alterations in invasiveness, cell motility and cell at tachment to fibronectin, collagen IV and laminin, Flow cytometric analysis with either peanut agglutinin (PNA) or Ricinus communis agglutinin (RCA) le ctin revealed that desialylated forms of glycoproteins on the cell surfaces were increased, In particular, a desialylated form of a cell surface glyco protein of 83 kDa was prominent in the transfectants, as determined by gala ctose oxidase labeling, These observations indicate that sialidase expressi on is inversely associated with metastatic potential and tumor growth in ca ncer cells, probably through a regulation mechanism that suppresses cell gr owth and anchorage-independent growth and promotes apoptosis with deprivati on of cell anchorage. (C) 2001 Wiley-Liss, Inc.