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.


CONCLUSIONS
CD44 v3-containing isoforms are associated with HNSCC growth, migration, and matrix metalloproteinase activity and can be identified in lymph node metastasis.
Wang
Steven J
SJ
Department of Otolaryngology-Head and Neck Surgery, Veterans Affairs Medical Center, University of California, San Francisco, California, USA. swang@ohns.ucsf.edu
Wreesmann
Volkert B
VB
Bourguignon
Lilly Y W
LY
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008198:Lymph Nodes / Q000378:metabolism*; D008207:Lymphatic Metastasis; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
D000911:Antibodies, Monoclonal; C121450:CD44V3,8-10; D016326:Extracellular Matrix Proteins; D018960:Hyaluronan Receptors; D020033:Protein Isoforms; D012333:RNA, Messenger; C098946:hyaluronan-mediated motility receptor; D020782:Matrix Metalloproteinases