LYSOSOMAL ALPHA-GLUCOSIDASE - CELL-SPECIF IC PROCESSING AND ALTERED MATURATION IN HT-29 COLON-CANCER CELLS

We have previously described the abnormal localization of resident Gol gi proteins and O-glycans in the rough endoplasmic reticulum of mucin- secreting HT-29 M6 colon cancer cells, suggesting altered protein traf ficking in these cells [Egea, Franci, Gambus, Lesuffleur, Zweibaum and Real(1993) J. Cell Sci. 105, 819-830]. In the present work, we have c hosen lysosomal alpha-glucosidase as a reporter to examine the intrace llular traffic of glycoproteins in M6 cells. We have compared the synt hesis and processing of alpha-glucosidase in mucin-secreting M6 cells and in Caco-2 colon cancer cells, the latter resembling normal absorpt ive intestinal epithelium. Our results show that alpha-glucosidase pro cessing and secretion is markedly delayed in M6 cells as compared with Caco-2 cells or normal fibroblasts, and this delay is caused by an ac cumulation of alpha-glucosidase precursor form in the trans-Golgi netw ork. Furthermore, treatment of Caco-2 cells with brefeldin A led to ch anges in alpha-glucosidase maturation similar to those observed in unt reated M6 cells. To determine whether altered processing occurs in oth er cultured cells, a panel of cancer cell lines and cultures from norm al exocrine pancreas were examined. In pancreas-derived cultures, alph a-glucosidase showed a processing pattern different from that describe d until now. Only HT-29 cells and HT-29-derived subpopulations display ed a defect in alpha-glucosidase maturation. In conclusion, alpha-gluc osidase processing is more diverse than has previously been described; this finding may have tissue-specific functional implications.