Role of CD44 Variant Exon 6 in Invasion of Head and Neck Squamous Cell Carcinoma

Abstract

OBJECTIVES: To determine the correlation between the expression of CD44 variant exon 6 (v6) and the clinicopathological features of head and neck squamous cell carcinomas (HNSCCs), and to study the role of CD44v6 in cell invasion using a human HNSCC cell line (HSC-2). DESIGN: The expression of CD44v6 was evaluated using immunohistochemical analysis in paraffin-embedded tissue specimens from 89 primary lesions. The concentration of CD44v6 protein in 37 cryopreserved tumor specimens was evaluated using the enzyme-linked immunosorbent assay. The HSC-2 cells were treated with 2F10, a monoclonal antibody against CD44v6. The effects of 2F10 on HSC-2 cell proliferation, migration, and invasion potential were evaluated. RESULTS: The down-regulation of CD44v6 expression or the concentration of cancer tissue significantly correlated with a lower degree of pathohistological differentiation and a higher rate of cervical metastasis. The invasion of HSC-2 cells into type I collagen gel and the expression of CD44v6 were decreased in invading cells released from the upper layer. Furthermore, the treatment of HSC-2 cells with 2F10 significantly enhanced cell invasion. However, 2F10 did not affect either the proliferation or migration properties of HSC-2 cells. CONCLUSIONS: The down-regulation of CD44v6 expression may be useful as a biological marker for the degree of malignancy in HNSCCs. We assume that the loss or dysfunction of CD44v6 is involved in the acquisition of invasion ability in HSC-2 cells. In addition, the potential existence of a CD44v6-mediated signal transduction pathway may play a role in inhibiting the invasion in HNSCCs.