OBJECTIVES/HYPOTHESIS
The CD44 family of receptors includes multiple variant isoforms, several of which have been linked to malignant properties including migration, invasion, and metastasis. The objective of this study was to investigate the role of the CD44 v3, v6, and v10 variant isoforms in head and neck squamous cell carcinoma (HNSCC) tumor progression behaviors.
STUDY DESIGN
Laboratory study involving cell cultures and clinical tissue specimens.
METHODS
Analysis of the expression of standard CD44s and the CD44 variant isoforms v3, v6, and v10 was carried out in the HNSCC cell line, HSC-3. The role of CD44 isoforms in migration, proliferation, and cisplatin resistance was determined. Immunohistochemical analysis was performed on clinical tissue specimens obtained from a series of 82 HNSCC patients. The expression of standard CD44s and the CD44 v3, v6, and v10 variants in primary tumor specimens (n=82) and metastatic cervical lymph nodes (n=24) were analyzed with respect to various clinicopathologic variables.
RESULTS
HSC-3 cells express at least 4 CD44 isoforms, and these CD44 isoforms mediate migration, proliferation, and cisplatin sensitivity. Compared to primary tumors, a significantly greater proportion of metastatic lymph nodes demonstrated strong expression of CD44 v3 (lymph node: 14/24 vs. primary tumor: 38/82), CD44 v6 (lymph node: 18/24 vs. primary tumor: 26/82), and CD44 v10 (lymph node: 14/24 vs. primary tumor: 16/82), while expression of standard CD44 was not significantly different in metastatic lymph nodes and primary tumors (lymph node: 10/24 vs. primary tumor: 60/82). Expression of CD44 variant isoforms were associated with advanced T stage (v3 and v6), regional (v3) and distant (v10) metastasis, perineural invasion (v6), and radiation failure (v10). CD44 v6 and CD44 v10 were also significantly associated with shorter disease-free survival.
CONCLUSION
CD44 isoforms mediate migration, proliferation, and cisplatin sensitivity in HNSCC. Furthermore, expression of certain CD44 variants may be important molecular markers for HNSCC progression, and should be investigated as potential therapeutic targets for therapy.