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Role of CD44 Variant Exon 6 in Invasion of Head and Neck Squamous Cell Carcinoma
Minoru Kanke, MD;
Masato Fujii, MD, PhD;
Kaori Kameyama, MD, PhD;
Jin Kanzaki, MD, PhD;
Yutaka Tokumaru, MD;
Yorihisa Imanishi, MD;
Toshiki Tomita, MD;
Yasuhiro Matsumura, MD, PhD
Arch Otolaryngol Head Neck Surg. 2000;126:1217-1223.
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.
From the Departments of Otolaryngology–Head and Neck Surgery (Drs Kanke, Fujii, Kanzaki, Tokumaru, Imanishi, and Tomita) and Pathology (Dr Kameyama), Keio University School of Medicine, and the Department of Medical Oncology, National Cancer Center Hospital (Dr Matsumura), Tokyo, Japan.
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