Claudin 1 overexpression increases invasion and is associated with aggressive histological features in oral squamous cell carcinoma

Abstract

BACKGROUND.The authors have previously shown that overexpression of claudin 1 (CLDN1) is associated with advanced disease stage in oral squamous cell carcinomas (OSCCs). Their goal was to examine CLDN1 expression in a large series of primary OSCCs and to further investigate whether CLDN1 overexpression plays a role in invasion in OSCC.METHODS.CLDN1 gene expression levels were determined by quantitative real‐time reverse transcription polymerase chain reaction (QRT‐PCR) in 100 primary OSCCs. CLDN1 protein expression was examined by immunohistochemistry in 70 of 100 OSCCs. E‐Cadherin protein levels were also assessed in 58 OSCCs. The authors performed a transwell Matrigel invasion assay for assessment of the invasive potential of CLDN1 overexpressing oral carcinoma cells. Western blotting and QRT‐PCR were used to assess CLDN1 expression in transfected cells and controls.RESULTS.CLDN1 mRNA was increased (median = 18.5) in 79 of 100 OSCCs, compared with normal oral mucosa (expression = 1.0). CLDN1 overexpression was associated with angiolymphatic (P = .037) and perineural invasion (P = .051). CLDN1 was highly expressed in 48 of 70 (68%) OSCCs. E‐Cadherin was lost or underexpressed in 49 of 58 (84%) OSCCs. The invasion assay showed that cells overexpressing CLDN1 have increased invasive potential, whereas small interfering RNA–mediated depletion of CLDN1 decreased the invasive potential of cells.CONCLUSIONS.CLDN1 overexpression is associated with angiolymphatic and perineural invasion, consistent with aggressive tumor behavior. Overexpression of CLDN1 protein is associated with increased invasiveness of oral carcinoma cells. Cancer 2008. © 2008 American Cancer Society.

Overexpression of Claudin-1 is Associated with Advanced Clinical Stage and Invasive Pathologic Characteristics of Oral Squamous Cell Carcinoma

“…In addition, the disagreement may also be a result of the differences in the methods of detection and the types of antibodies used with varying cross-reactivity potential. Nonetheless, in conjunction with our finding, Dos Reis et al [33] found that the increased claudin-1 gene expression was associated with the increased angiolymphatic and perineural invasions, the prognostically relevant histopathologic features of OSCC [2].…”

“…A handful of studies reported the altered claudin-1 expression in OSCC [25,31,33]. Compared to the normal oral mucosa, claudin-1 expression was altered in different grades of oral epithelial dysplasia and squamous cell carcinoma [26,31].…”

“…The potential role of claudin-1 in promoting the growth and invasion of OSCC cells was reported [32][33][34]. However, no study has shown the association of claudin-1 and claudin-4 protein expression in OSCC and clinical prognostic factors.…”

Prox1 and FOXC2 Act as Regulators of Lymphangiogenesis and Angiogenesis in Oral Squamous Cell Carcinoma

“…OSCC has a high potential for local invasion and nodal metastasis and over 80% of early stage OSCC patients can be rescued by treatment, whereas less than 70% of advanced stage OSCC patients are incurable. The overall 5-year survival rates of OSCC have not improved significantly in the past 30 years, and it remains less than 50% [6]–[8]. Therefore, early detection and elucidation of the detailed molecular mechanism of OSCC are important.…”

Mechanisms of Invasion in Head and Neck Cancer

“…130,131 Desmosomes are another cell-cell adhesion structure, which can suppress invasion. 132 However, overexpression of certain adhesion proteins, such as claudin 1 133 and desmoglein 3, 134 can enhance invasion. Although degradation of the ECM, especially the basement membrane, is a key property of invasive tumors, interaction with the ECM is also important for invasion and prognosis.…”