CD44 REGULATES HEMATOPOIETIC PROGENITOR DISTRIBUTION, GRANULOMA-FORMATION, AND TUMORIGENICITY

CD44 is expressed in various isoforms on numerous cell types and tissu es during embryogenesis and in the mature organism. CD44 may also be i nvolved in tumor growth. To study the multiple roles of CD44, we aboli shed expression of all known isoforms of CD44 in mice by targeting exo ns encoding the invariant N-terminus region of the molecule. Surprisin gly, mice were born in Mendelian ratio without any obvious development al or neurological deficits. Hematological impairment was evidenced by altered tissue distribution of myeloid progenitors with increased lev ers of corony-forming unit-granulocyte-macrophage (CFU-GM) in bone mar row and reduced numbers of CFU-GM in spleen. Fetal liver colony-formin g unit-spleen and granulocyte colony-stimulating factor mobilization a ssays, together with reduced CFU-GM in peripheral blood, suggested tha t progenitor egress from bone marrow was defective. Tn what was either a compensatory response to CD44 deficiency or an immunoregulatory def ect, mice also developed exaggerated granuloma responses to Cryotospor idium parvum infection. Finally, tumor studies showed that SV40-transf ormed CD44-deficient fibroblasts were highly tumorigenic in nude mice, whereas reintroduction of CD44s expression into these fibroblasts res ulted in a dramatic inhibition of tumor growth. (C) 1997 by The Americ an Society of Hematology.