Intracellular claudin‐1 at the invasive front of tongue squamous cell carcinoma is associated with lymph node metastasis

• Published in: Cancer science Vol. 111; no. 2; pp. 700 - 712
• Main Authors: Yamamoto, Daisuke, Kayamori, Kou, Sakamoto, Kei, Tsuchiya, Maiko, Ikeda, Tohru, Harada, Hiroyuki, Yoda, Tetsuya, Watabe, Tetsuro, Hara‐Yokoyama, Miki
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.02.2020; John Wiley and Sons Inc
• Subjects: Anoikis; Biomarkers, Tumor - metabolism; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Cell adhesion & migration; Cell Line, Tumor; Cell migration; Cell surface; Claudin-1 - metabolism; claudin‐1; Colon; Colorectal cancer; CRISPR; Disease Progression; endocytosis; Epithelial cells; Female; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Intracellular; invasion front; Invasiveness; Localization; Lymph nodes; Lymphatic Metastasis; Lymphatic system; Male; Medical prognosis; Metastases; Metastasis; Motility; Neoplasm Invasiveness; Oral cancer; Original; Polarity; Proteins; Squamous cell carcinoma; Tight junctions; Tongue; Tongue Neoplasms - metabolism; Tongue Neoplasms - pathology; tongue squamous cell carcinoma; Transport Vesicles - metabolism; Tumor necrosis factor-TNF; Up-Regulation; endocytosis; claudin-1; invasion front; metastasis; tongue squamous cell carcinoma
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/cas.14249

Claudins are the major component of tight junctions, which form a primary barrier to paracellular diffusion and maintain cell polarity in normal epithelia and endothelia. In cancer cells, claudins play additional roles besides serving as components of the tight junctions, and participate in anoikis or invasion. Among the claudin family proteins, claudin‐1 has the most promising potential, both diagnostically and prognostically, in many types of cancers, including oral, gastric, liver, and colon cancers. However, conflicting results have been reported in relation to the degree of claudin‐1 expression and the prognosis, suggesting that the expression level of claudin‐1 alone is not sufficient to analyze the relationship between claudin‐1 and cancer progression. As endocytic trafficking of claudin‐1 has been reported in several epithelial cell types in vitro, we aimed to determine whether intracellular localization of claudin‐1 is the missing aspect between claudin‐1 and cancer. We investigated the expression of claudin‐1 in 83 tongue squamous cell carcinoma (TSCC) pathological specimens. Although the expression level of claudin‐1 based on immunohistochemistry was not associated with TSCC progression, within the high claudin‐1 expression group, the incidence of intracellular localization of claudin‐1 was correlated with cervical lymph node metastasis. In an in vitro experiment, claudin‐1 was constitutively internalized in TSCC‐derived cells. Motility of TSCC‐derived cells was increased by deficiency of claudin‐1, suggesting that the decrease in cell‐surface claudin‐1 promoted the cell migration. Therefore, intracellular localization of claudin‐1 at the invasion front may represent a promising diagnostic marker of TSCC. Claudin‐1 was predominantly localized at the membrane in the center of the lesion, but intracellular claudin‐1 localization was also observed at the invasion front in some tongue squamous cell carcinoma (TSCC) pathological specimens. Within the high claudin‐1 expression group, incidence of intracellular localization of claudin‐1 correlated with cervical lymph node metastasis.