GROWTH AS A SOLID TUMOR OR REDUCED GLUCOSE-CONCENTRATIONS IN CULTURE REVERSIBLY INDUCE CD44-MEDIATED HYALURONAN RECOGNITION BY CHINESE-HAMSTER OVARY CELLS

The density, molecular isoform, and posttranslational modifications of CD44 can markedly influence growth and metastatic behavior of tumors. Many CD44 functions, including some involving tumors, have been attri buted to its ability to recognize hyaluronan (HA). However, only certa in CD44-bearing cells bind soluble or immobilized HA. We now show that CD44 made by wild-type Chinese hamster ovary (CHO-KI) cells and a lig and-binding subclone differ with respect to N-linked glycosylation. Wh ile both bear CD44 with highly branched, complex-type glycoforms, CD44 expressed by the wad type was more extensively sialylated, CHO-KI cel ls which failed to recognize HA when grown in culture gained this abil ity when grown as a solid tumor and reverted to a non-HA-binding state when returned to culture, The ability of CHO-K1 cells to recognize HA was also reversibly induced when glucose concentrations in the medium were reduced. Glucose restriction influenced CD44-mediated HA binding by many but not ail, of a series of murine tumors. Glucose concentrat ions and glycosylation inhibitors only partially influenced CD44 recep tor function on resting murine B lymphocytes. These observations sugge st that glucose levels or other local environmental conditions may mar kedly influence glycosylation pathways used by some tumor cells, resul ting in dramatic alteration of CD44-mediated functions.