INVOLVEMENT OF CD44 ISOFORMS IN TUMOR-CELL INVASION AND METASTASIS

CD44 is a transmembrane glycoprotein ; one of its normal functions may relate to the activation of T-and B-cells and the homing of lymphocytes. The other major role is as a hyaluronan receptor, playing an important part in the uptake and degradation of this glycosaminoglycan. The standard form of CD44, CD44H, probably enhances the tumorigenic properties of some melanomas. Further investigations carried out with a rat pancreatic adenocarcinoma revealed that CD44 occurs in numerous splice variants and that the metastasis specific epitope is derived from exon v6. Expression of the CD44v6 epitope is also seen in human tumors, thus this marker has potential for prognosis and possibly for therapy. On the basis of the physiological functions and molecular interactions of CD44, several mechanisms can be assumed to explain the role of CD44 in invasion and/or metastasis. Among them, the most interesting are related to (1) the elaboration and organisation of an extracellular matrix facilitating tumorigenicity, (2) antitumoral immunity linked to costimulation involving several molecular signals or (3) modifications of motility and adhesion of metastatic cells. Future prospects regarding immunotherapy, must be restrained because CD44 seems to be involved in the early steps of metastatic dissemination, often before clinical expression of the tumor. On the other hand, preliminary clinico-biological studies demonstrate that CD44 is a potential marker for prognosis in the case of gastric and colorectal cancers.