Role of CD44 variant exon 6 in invasion of head and neck squamous cell carcinoma.
OBJECTIVE
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).


METHODS
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.
Kanke
M
M
Department of Otolaryngology-Head and Neck Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Fujii
M
M
Kameyama
K
K
Kanzaki
J
J
Tokumaru
Y
Y
Imanishi
Y
Y
Tomita
T
T
Matsumura
Y
Y
D015415:Biomarkers / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology*; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D005091:Exons; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics*; D007150:Immunohistochemistry; D009361:Neoplasm Invasiveness / Q000235:genetics*; D014407:Tumor Cells, Cultured
D015415:Biomarkers; D018960:Hyaluronan Receptors