Regulation of Fas mediated apoptosis by CD44

Over the last decade, apoptosis has grown from an obscure process to a complex and interesting scientific field, and many players have been identified. One of the basic features of malignant transformation and autoimmunity is the acquisition of resistance to apoptosis. Many reports suggest that CD44 variant isoforms exhibit an anti-apoptotic effect leading to the progression of cancer and inflammatory diseases. However the molecular mechanisms of CD44s and CD44v actions have so far not been elucidated. Moreover literature about CD44 is controversial, some researchers describe CD44 as a survival molecule, others as a pro-apoptotic protein. Probably, this controversy is due to the presence of several isoforms and it might be possible that isoforms exhibit different and/or even opposite functions. The aims of this study were to elucidate the following questions: 1) Are CD44 standard and/or variant isoforms regulating Fas-mediated apoptosis and how? (Chapter I and II). 2) Which is the in vivo implication of CD44 variant isoforms in autoimmune diseases such as multiple sclerosis and experimental autoimmune encephalomyelitis? (Chapter III). To find an answer to these questions will improve our understanding of the pathogenesis of life threatening diseases such as cancer and autoimmunity, and may open new treatment strategies.