CD44 family and gynaecological cancer

CD44 refers to a multifunctional family of type I transmembrane proteins. The CD44 gene contains at least 21 exons, 11 of which can be variably spliced and produce a variety of heavily glycosylated cell surface proteins, known as CD44 variant isoforms. These proteins have been implicated in many biological processes, such as cell adhesion, cell substrate, cell to cell interactions, including lymphocyte homing haemopoiesis, cell migration and metastasis. These abilities are of great importance in chronic inflammation and in cancer. Published data have shown that CD44 has the ability to recruit leucocytes to vascular endothelium at sites of inflammation, which is one of the first steps in the inflammatory response. In cancer, deregulation of the adhesion mechanisms increases the ability of tumor cells to metastasis. This behavior seems to be explained by the existing relationship between hyaluronan, a basic component of the extracellular matrix and CD44, which is its major cell surface receptor. There are CD44 variant isoforms which are expressed on different types of normal cells. In addition some isoforms are overexpressed on tumor cells including breast, cervical, endometrial and ovarian cancer. This property seems to be correlated with the metastatic potential of these cells. This review summarizes the available data on the possible prognostic role of the polymorphic CD44 protein family and its role as a tumor marker in gynaecological cancer.