Oncostatin M and transforming growth factor-beta 1 induce post-translational modification and hyaluronan binding to CD44 in lung-derived epithelial tumor cells

CD44, a receptor for hyaluronan (HA), has been implicated in tumor growth a nd metastasis. Most CD44-positive cells fail to exhibit constitutive HA rec eptor function but CD44-mediated HA binding on hematopoetic cells can be in duced by antibody cross-linking of the receptor and by physiologic stimuli, including cytokines. me now demonstrate that oncostatin M (OSM) and transf orming growth factor-beta 1, cytokines known to regulate the growth of tumo r cells, stimulate HA binding in lung epithelial-derived tumor cells. In lu ng epithelial-derived tumor cells, cytokine-induced binding resulted from p ost-translational modification of the receptor. OSM-induced HA binding was associated with a reduction in N-linked carbohydrate content of CD44. In ad dition, OSM induced Hcl binding via a novel mechanism requiring sulfation o f chondroitin sulfate chains linked to CD44. The mechanism underlying trans forming growth factor-beta 1 induced HA binding was distinct from the effec ts of OSM. The data presented indicate that modulation of the glycosylation and sulfation of CD44 by cytokines provides mechanisms for regulating cell adhesion during tumor growth and metastasis.