Tight junctional (TJ) proteins create a seal between adjacent polarized epithelial cells, which ensures proper tissue barrier function. The claudin-based junctions are not static and undergo continuous molecular remodeling, and include other TJ proteins, as ZO-1/2 and Occludin, and tyrosine kinase (TK) receptors such as VEGFR2. Claudin3 is an integral component of the tight junction proteins in polarized epithelia. The expression of claudin3 was assessed in epithelial-derived tumors using Oncomine database. To determine the gene alteration during carcinogenesis, copy number alterations and mutations of claudin3 were evaluated using cBioPortal database. Claudin3 is overexpressed in several tumors including gynecological, bladder, breast and prostate carcinomas. 38% of the 163 evaluated studies show mutations and/or amplification of claudin3. 3D reconstruction of tissue samples following immunofluorescence analysis clearly demonstrated that, unlike in healthy tissues, claudin3 is mislocalized and unengaged in the formation of tight junction in tumor samples. These data strongly support the evaluation of unengaged claudin3 as a target for the development of novel diagnostic probes, optical approaches for real time detection of tumoral tissues during surgery, and target therapeutic drugs.
Evaluation of Paracellular Permeability in VEGFR2 Mutants Patient-Derived Organoid
Michela Corsini;Elisabetta Grillo;Margherita Di Somma;Stefania Mitola
2017-01-01
Abstract
Tight junctional (TJ) proteins create a seal between adjacent polarized epithelial cells, which ensures proper tissue barrier function. The claudin-based junctions are not static and undergo continuous molecular remodeling, and include other TJ proteins, as ZO-1/2 and Occludin, and tyrosine kinase (TK) receptors such as VEGFR2. Claudin3 is an integral component of the tight junction proteins in polarized epithelia. The expression of claudin3 was assessed in epithelial-derived tumors using Oncomine database. To determine the gene alteration during carcinogenesis, copy number alterations and mutations of claudin3 were evaluated using cBioPortal database. Claudin3 is overexpressed in several tumors including gynecological, bladder, breast and prostate carcinomas. 38% of the 163 evaluated studies show mutations and/or amplification of claudin3. 3D reconstruction of tissue samples following immunofluorescence analysis clearly demonstrated that, unlike in healthy tissues, claudin3 is mislocalized and unengaged in the formation of tight junction in tumor samples. These data strongly support the evaluation of unengaged claudin3 as a target for the development of novel diagnostic probes, optical approaches for real time detection of tumoral tissues during surgery, and target therapeutic drugs.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
