Abstract
Problem
The CD44 family of receptors includes multiple variant isoforms, several of which have been linked to tumor progression. The objective of this study was to investigate the role of CD44 v6- and v10-containing isoforms in head and neck squamous cell carcinoma (HNSCC) progression.
Methods
A laboratory investigation utilizing a panel of 13 HNSCC cell lines and clinical tissue specimens from a series of 82 patients with HNSCC was performed.
Results
Immunohistochemical analysis of 82 primary HNSCC tumors and 24 metastatic lymph nodes revealed expression of CD44 v6 and v10 variants. A greater proportion of metastatic lymph nodes vs. primary tumors demonstrated strong expression of CD44 v6 (18/24 vs. 26/82) and CD44 v10 (14/24 vs. 16/82), while expression of standard CD44 was not significantly different in metastatic lymph nodes and primary tumors (10/24 vs 60/82). In addition, greater than expected expression of CD44 v10 was found among 14 specimens obtained from patients previously treated with chemoradiation. To further analyze the role of these CD44 variants in HNSCC progression, HNSCC cell lines were selected on the basis of their CD44 v6 and v10 expression. A HNSCC cell line without CD44 expression and cells of the same variant-expressing cell lines transfected with short-hairpin RNA for CD44 were used as controls. Compared to controls, HNSCC cells expressing CD44 v6-containing isoforms demonstrated increased hyaluronan-mediated tumor cell growth and migration. Furthermore, HNSCC cells expressing CD44 v10-containing isoforms demonstrated increased hyaluronan-mediated cisplatin resistance.
Conclusion
CD44 v6- and v10-containing isoforms are associated with HNSCC progression.
Significance
CD44 v6- and v10-containing isoforms may be useful tumor markers and targets for HNSCC therapy.
Support
This work was supported by an AAO-HNS/AHNS Young Investigator Award.
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