Tuesday 17 June 2003
Definition: CD44 is a well characterized cellular adhesion molecule involved in several human malignancies. It is encoded by a gene located at 11p12-13.
CD44 binds hyaluronan. Mucin-like glycoproteins, such as heparan sulfate, serve as ligands for the leukocyte adhesion molecule called CD44. These glycoproteins are found in the extracellular matrix and on cell surfaces.
CD44 is expressed by lymphoid cells, and is involved in the extravasation of lymphoid cells, it does not appear to be involved in the sequestration or transport of HA by lymphatic vessels.
CD44 is a widely distributed integral membrane glycoprotein, which is expressed as a multitude of isoforms generated by alternative splicing of at least 10 different variant exons and post-translational modifications.
CD44 is currently thought to be the principal cell surface receptor for hyaluronate (hyaluronic acid), the major component of the extracellular matrix.
The adhesion molecule CD44 (CD44s; CD44H) and its isoforms (CD44v3-6 and v9) are preferentially expressed by different cell types. These transmembrane glycoproteins are involved in cell-cell and cell-matrix interactions and in cell trafficking and, thus, may play a role in tumor metastasis and/or local invasion.
The expression pattern of CD44s and variant isoforms, particularly CD44v6 and CD44v9, of some neoplasms, including soft tissue tumors, correlates with clinical course and outcome.
Overexpression of isoform CD44v6 correlates with amplification at 11p12-13 in diffuse-type gastric adenocarcinomas.
CD44 targeting reduces tumour growth and prevents post-chemotherapy relapse of human breast cancers xenografts. Marangoni E, Lecomte N, Durand L, de Pinieux G, Decaudin D, Chomienne C, Smadja-Joffe F, Poupon MF. Br J Cancer. 2009 Mar 24;100(6):918-22. PMID: 19240712
Carvalho R, Milne AN, Polak M, Offerhaus GJ, Weterman MA. A novel region of amplification at 11p12-13 in gastric cancer, revealed by representational difference analysis, is associated with overexpression of CD44v6, especially in early-onset gastric carcinomas. Genes Chromosomes Cancer. 2006 Oct;45(10):967-75. PMID: 16868940
Montgomery E, Abraham SC, Fisher C, Deasel MR, Amr SS, Sheikh SS, House M, Lilliemoe K, Choti M, Brock M, Ephron DT, Zahuruk M, Chadburn A. CD44 loss in gastric stromal tumors as a prognostic marker.
Am J Surg Pathol. 2004 Feb;28(2):168-77. PMID: 15043305