We concluded that combined modulation of Wnt/Dkk-3/claudin-5 and TLR-4 pathways, simultaneously targeting apoptosis and survival signaling defects, might shift the balance from tumor growth stasis to cytotoxic therapeutic responses, flowing in greater therapeutic benefits.
Quantitative analysis of the transcript and protein expression data showed that CLDN1 and CLDN5 were significantly down regulated (p=<0.001) in tumors of all four grades and model cell lines.
In the single HER2+ tumor when compared with the other subtypes CLDNs 5, 16, 17, 18, CTNNAL1, JAM-B, ZO-1, ZO-2 and PARD3 genes were found to be upregulated.
Under-expression of the tight junction proteins occludin, claudin-1 and claudin-5 are key molecular abnormalities responsible for the increased permeability of tumour endothelial tight junctions.