HISTOLOGY AND HISTOPATHOLOGY

Cellular and Molecular Biology

 

N-cadherin expression is involved in malignant behavior of head and neck cancer in relation to epithelial-mesenchymal transition

Phuong Thao Nguyen1, Yasusei Kudo1, Maki Yoshida1, Nobuyuki Kamata2, Ikuko Ogawa3 and Takashi Takata1

1Department of Oral and Maxillofacial Pathobiology, Division of Frontier Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Japan, 2Department of Oral and Maxillofacial Surgery, Division of Cervico-Gnathostomatology, Graduate School of Biomedical Sciences, Hiroshima University, Japan and 3Center of Oral Clinical Examination, Hiroshima University Hospital, Japan.

Offprint requests to: Yasusei Kudo, D.D.S., PhD, Department of Oral and Maxillofacial Pathobiology, Division of Frontier Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Japan, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan. e-mail: ykudo@hiroshima-u.ac.jp and Takashi Takata, D.D.S., PhD, Department of Oral and Maxillofacial Pathobiology, Division of Frontier Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Japan, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan. e-mail: ttakata@hiroshima-u.ac.jp


Summary. The loss of E-cadherin and the gain of N-cadherin expression are known as “cadherin switching”. Cadherin switching is a major hallmark of epithelial-mesenchymal transition (EMT). EMT is a crucial process in cancer progression, providing cancer cells with the ability to escape from the primary focus, to invade stromal tissues and to migrate to distant regions. Although down-regulation of E-cadherin is well known in various cancers, there are a few studies on N-cadherin expression in cancer. Here, therefore, we investigated whether N-cadherin expression was associated with the progression of head and neck squamous cell carcinoma (HNSCC). First, we examined the expression of N-cadherin by immunohistochemistry and its correlation with clinico-pathological findings. High expression of N-cadherin was observed in 52 of 80 HNSCC cases and was significantly correlated with malignant behaviors. Next, we examined the correlation between N-cadherin and E-cadherin. Cadherin switching (high expression of N-cadherin and low expression of E-cadherin) was found in 30 of 80 HNSCC cases and was well correlated with histological differentiation, pattern of invasion and lymph node metastasis in HNSCC cases. Moreover, we examined the expression of N-cadherin and E-cadherin by RT-PCR in 16 HNSCC cell lines to confirm the immunohistochemical findings. N-cadherin expression was observed in 7 of 16 HNSCC cells, and cadherin switching was observed in 2 HNSCC cells. Interestingly, HNSCC cells with cadherin switching have EMT features. In conclusion, we suggest that i) N-cadherin may play an important role in malignant behaviors of HNSCC, and ii) cadherin switching might be considered as a discrete critical event in EMT and metastatic potential of HNSCC
. Histol Histopathol 26, 147-156 (2011)

Key words: N-cadherin, E-cadherin, EMT, Invasion, Head and neck squamous cell carcinoma

DOI: 10.14670/HH-26.147