94 Experimental Oncology 28, 94–98, 2006 (June) THE STRUCTURE AND FUNCTION OF CD�� CD�� ADHESION MOLECULE The CD44 proteins form widely expressed family of adhesion molecules involved in cell-cell and cell-matrix interactions. It was shown that aberrant expression of CD44 and its variant forms is associated with invasive and metastatic potential of cancer cells as well with poor prognosis in several types of human cancer. This family of transmembrane glucoproteins is identified as a large number of isoforms with a common stable main molecular part. The main structure of molecule consists of N-terminal extracellular domain, memb- rane proximal region, transmembrane domain and cytoplasmatic tail. This consistent structure of trans- This consistent structure of trans- membrane protein shares many characteristics with basic structures of other known adhesion molecules. The CD44 and its isoforms have been detected in many types of normal human tissue, predominantly in the skin, gingiva and tongue, larynx, esophagus, cervix, bladder, pancreas, and parotid gland. The most com- mon isoform of this molecule, CD44s (s for standard) is also ubiquitously present in hematopoietic tissues and gastrointestinal tract epithelium. The CD44 gene is unique for all the various iso- forms of the protein. It was mapped in chromosome 11p13 and includes at least 19 exons. Exons 1–5 and 16–19 are spliced together to form transcript, known as CD44s isoform, predominantly presented in hae- matopoietic tissues. Exons 6–15 are variable exons, alternatively spliced in insertion site between 5 and 16, generating various isoforms of molecule [1, 2]. These variable exons are identified as v1–v10, respectively. The extracellular domain of standard form consists of 270 amino acid chain, folded into globular tertiary structure by disulphide bonds between three pairs of cysteine residues on its N-terminus. These cys- teine residues are very important for the stability of molecule and seem to be required for correct folding and for hyaluronan binding [3]. This terminal domain is encoded by exons 1–5 and serves as the main ligand-binding site of CD44 molecule. The following membrane proximal region, encoded by exons 16 and 17, includes several carbohydrate modification sites. The hydrophobic transmembrane domain, consisting of 21 amino acids, is encoded by exon 17. Cytoplasmic part of the molecule, consisting of 72 amino acids, is encoded by exons 17, 18, 19. The variable regions of CD44 molecule are inserted in alternative splicing site, encoded by exons v1–v10 [3]. The expected molecular weight of CD44 molecule, as estimated from the number of amino acid residues, is much lower than the molecular mass measured by gel electrophoresis (80 kDa versus 200 kDa). This is the result of extended post- translational modification of CD44 isoforms [4]. Special potential modifica- tion sites, predominantly glucosylation sites, exist in membrane proximal extracellular region as previously noticed, but also in the N-terminal ectodomain and in the variable exon products of the molecule [5]. The degree of glucosylation can affect the ligand binding features of the protein and alter its function. Observa- tions indicate that changes in glucosylation of CD44 can affect its interaction with hyaluronic acid (HA). So this posttranslational modification may provide impor- tant regulatory mechanism for CD44 functioning [6]. In addition, various isoforms of CD44 molecule have different ability to bind HA. Therefore, via alternative splicing and glucosylation processes, CD44 is involved in the HA binding regulation and even degradation of this giant molecule [7]. It is well known that the first five exons of CD44 encode globular protein domain, which contains motifs that function as docking sites for several substances of extracellular matrix. Apart from hyaluronan, collagen, laminin and fibronectin, CD44 seems to promote matrix dependent migration, as it was demonstrated in experiments in vitro [8]. However, there is no evidence with in vivo studies to confirm previously mentioned data. Thus, separately from hyaluronan binding site, these binding sites were not mapped precisely. Different functions of CD44 molecule and its iso- forms are mediated through its main ligand HA and THE ROLE OF CD�� ADHESION MOLECULE IN ORAL CAVITY CANCER A. Georgolios 1, 2 , A. Batistatou 3 , A. Charalabopoulos 1, 4 , L. Manolopoulos 2 , K. Charalabopoulos 1, * 1 Department of Physiology, Division of Adhesion Molecules, Ioannina University Medical School, Ioannina, Greece 2 Department of Otorhinolarygology, Athens University Medical School, Athens, Greece 3 Department of Pathology, Ioannina University Medical School, Ioannina, Greece 4 Department of Surgery, Peterborough & Stamford Hospitals, Cambridgeshire, United Kingdom CD44 � � ������ �������� ����� � � �� � ����� �� ���������� ���� � ��� � �������� � ���� � ������� � ��� ���� � � ������ �������� ����� � � �� � ����� �� ���������� ���� � ��� � ���� ���� � ���� � ������� � ��� ���� � ������� � ��� ���� ���� ��� � ��������� � ���� �x���� � ��������� ���� �� q����� ���� ���� ������. T�� �v��� � ����� � � �� ��� � CD44 � CD44 � � � �� ��������� � � �� ��� ��v��� ��� � ������ ������ � �� �������� �� � ������ �� ����� � ���� � ��� ��v���. Key Words: ������ �������� CD44 ��� ���� ���� ��k ����. Received: March 29, 2006. *Correspondence: �a�: � 26� �0 9���0 �a�: � 26� �0 9���0 E-mail: kcharala@cc.uoi.gr Abbreviation used: � h�aluronic acid. � h�aluronic acid. Exp Oncol 2006 28, 2, 94–98 REVIEW