Association of CD44 V3‐containing isoforms with tumor cell growth, migration, matrix metalloproteinase expression, and lymph node metastasis in head and neck cancer

Background. The CD44 family of receptors includes multiple variant isoforms, some of which have been linked to tumor progression. The objective of this study was to investigate whether CD44 v3‐containing isoforms are involved in head and neck squamous cell carcinoma (HNSCC) tumor progression. Methods. Laboratory investigation utilizing HNSCC cell lines and clinical tissue specimens was performed. Results. Investigation of 13 HNSCC cell lines revealed a diversity of CD44 isoform profiles, including expression of CD44 v3‐containing isoforms. Two cell lines, HOC313 and MDA1483, were selected for further study based on their CD44 v3 expression profile. The HOC313 cell line, which highly expresses CD44 v3‐containing isoforms, demonstrated hyaluronan‐mediated CD44‐dependent promotion of tumor cell growth and migration. Conditioned media from the HOC313 cell line also exhibited high matrix metalloproteinase expression on gelatin zymography. Immunohistochemical analysis of a series of metastatic HNSCC lymph nodes revealed CD44 overexpression as well as staining for CD44 v3‐containing isoforms. Conclusion. CD44 v3‐containing isoforms are associated with HNSCC growth, migration, and matrix metalloproteinase activity and can be identified in lymph node metastasis. © 2007 Wiley Periodicals, Inc. Head Neck, 2007