Expression profile of Claudins 3, 4, and 7 in breast tumors and its correlation with clinicopathological features

Abstract

Claudins, integral components of tight junctions, play a pivotal role in maintaining cellular adhesion and polarity. Aberrant expression of claudins has been implicated in the progression of various malignancies, including breast cancer (BC). This study aims to elucidate the clinical relevance of claudins by studying the expression of Claudins 3, 4, and 7 in BC cell lines (CLs) and cancer tissues and correlating it with cellular properties and clinicopathological parameters. The transcriptional expression of Claudins 3, 4, and 7 was assessed in four BCCLs (MDA-MB-231, MDA-MB-468, T47D, and SKBR-3) and tumor tissues by using quantitative PCR. Correlations between claudin expression profiles and clinicopathological parameters, including tumor grade, lymph node involvement, and proliferative index, were evaluated in patient samples. Compared to normal breast tissue, all BCCLs exhibited downregulated expression of Claudins 3, 4, and 7. Differential expression was observed among CLs, with MDA-MB-231 exhibiting the lowest and MDA-MB-468 the highest levels. Among BC patient samples (n = 65), 97% demonstrated significant (P < 0.05) dysregulation in the expression of one or more of these claudins. Prevalence of Claudins 3, 4, 7-low and -high tumors was found to be 29.23% and 21.53% respectively, in our patients. The former correlated significantly with adverse prognostic factors, including higher grade, nodal metastasis, and elevated proliferative indices. The pharmacological induction of Claudin 4 by celecoxib was found to attenuate cell viability, proliferation, and migration in aggressive claudin-low BC cells. These findings underscore the potential utility of modulating claudins as a therapeutic strategy for managing claudin-low BCs.

Keywords: BC; claudin-low tumors; claudins; stemness.