Joint detection of claudin‐1 and junctional adhesion molecule‐A as a therapeutic target in oral epithelial dysplasia and oral squamous cell carcinoma

Abstract

Abnormal expression of claudin‐1 (CLDN‐1) and junctional adhesion molecule‐A (JAM‐A) has been described in certain malignancies but their clinical relevance is poorly understood. The present study aims to elucidate the role of CLDN‐1 and JAM‐A in oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC). Changes in the expression of these proteins were identified immunohistochemically on tissue sections from patients with OED and OSCC and compared with control. A correlation between the expression level of proteins and clinicopathological features was analyzed by Pearson's correlation χ2 test. The survival curve of the follow‐up data was estimated by the Kaplan‐Meier method followed by the log‐rank test. CLDN‐1 and JAM‐A were highly expressed in OED and OSCC tissues when compared to control. Also, delocalization of CLDN‐1 from the membrane to the cytoplasm to the nucleus was observed as the cell proceeds from normal to malignancy. Increased expression of CLDN‐1 and JAM‐A in both OED and OSCC were concomitant with histological grades. In addition, increased JAM‐A was associated with perineural invasion of cancer cells. A positive correlation between the expression level of proteins was observed in OED (r = 0.733) and OSCC (r = 0.577). Kaplan‐Meier analysis in patients with OSCC showed that the survival rate was lower in patients with high CLDN‐1 and high JAM‐A expression compared to low expressed patients. To conclude, the elevated level and delocalization of CLDN‐1 and JAM‐A suggest their use as tumor markers. A positive correlation between CLDN‐1 and JAM‐A suggests joint detection of these proteins as a future diagnostic tool in oral precancerous and cancerous conditions.

Interplay between tumor microenvironment and partial EMT as the driver of tumor progression

“…Collective migration is observed in many aggressive cancers in which a group of cells maintain a coordinated movement guided by the cues from the microenvironment (Yang et al, 2019b). Contrary to the migratory single cells that exhibit complete loss of cell-cell adhesion, migratory cell clusters preserve cell-cell junctions principally through ECAD (Singh et al, 2016(Singh et al, , 2019, gap junctions (Citi et al, 2014;Kuznik et al, 2016;Park et al, 2016;Leech et al, 2018;Upadhaya et al, 2019;Zhang et al, 2020), and surface adherent proteins from the immunoglobulin family (Friedl et al, 2012;Aiello et al, 2018).…”

Intestinal Barrier, Claudins and Mycotoxins

“…Numerous studies reported that claudin-1 play a significant role in this type of cancer and its elevated expression is observed in most oral, carcinomas. Moreover, the higher the expression, the more advanced stage tumors are diagnosed, and what is worth emphasizing-it is also associated with a lower survival rate [54][55][56][57]. Patricia Pintor Dos Reis et al showed that overexpression of CLDN1 is associated with higher invasion of cells and aggressiveness observed in immunohistochemistry [58].…”

The F11 Receptor (F11R)/Junctional Adhesion Molecule-A (JAM-A) (F11R/JAM-A) in cancer progression

“…Recently, the F11R/JAM-A protein expression was investigated by Upadhaya et al [ 127 ] in oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC). Revealed F11R/JAM-A overexpression was related to cancer cell perineural invasion, aggressive histological tumor grades, and correlated with a low survival rate in comparison to cancer patients with F11R/JAM-A underexpression.…”

“…The authors suggested that the dimerization mechanism is responsible for the high F11R/JAM-A level. In most OSCC tissues, F11R/JAM-A was delocalized to the cytoplasm from the cell membrane [ 127 ].…”