Changes of cell adhesion and extracellular matrix (ECM) components in cervical intraepithelial neoplasia

Abstract

Cell-cell and cell-extracellular matrix interaction is crucial in tumor progression. Tight junction (TJ) proteins as occludin and claudins (CLDNs) play important role in this process together with several extracellular matrix components, as syndecan. Our previous work suggested significant changes in the expression of claudins even in the early stages of cervical carcinogenesis. The aim of our present work was to study the expression of occludin and syndecan-1, as compared to CLDNs, in early phases of cervical carcinogenesis. Paraffin sections of 50 samples were studied by immunohistochemistry, including cervical intraepithelial neoplasias (CINI-II-III), in situ carcinomas (CIS) and normal cervical samples. Occludin and CLDN-2 were found colocalized in the basal layer, while syndecan-1 and CLDN-1, -4 and -7 were coexpressed in the parabasal and intermedier layers in normal epithelia. Intensity of occludin staining decreased in CIN/CIS lesions, although it was more extended towards the upper epithelial layers with inverse relation with grades, as seen in the case of CLDN-2 expression. CLDN-1, -2, -4 and -7 were detected in the entire epithelium in CIN, showing decrease in CIS. The progression of CIN was associated with reduced syndecan-1 expression, in contrast to CLDN-1, -4 and -7 which increased toward CIS. The obtained data suggest that significant changes occur in the composition of cell adhesion complexes even in early stages of cervical carcinogenesis. The pattern of expression is characteristic for the alteration, the changes in the different components, however, are not parallel with each other.

Second harmonic generation microscopy: principles and applications to disease diagnosis

“…Moreover, 85% of all cancers are epithelial in nature, and there is increasing evidence that remodeling of the underlying ECM may be a common aspect of carcinogenesis. For example, cervical pre-cancer has early changes in structural protein assembly prior to cancer [77], ii) in prostate there is alteration in the stromal microenvironment which is sufficient to promote malignant transformation of the epithelial cells [78]; iii) colon studies have shown that the ECM and the conditioned medium from colon carcinoma support and catalyze the conversion of normal epithelial to carcinoma cells [79]; and iv) Jain observed increased collagen in a mouse model of human melanoma [80].…”

Biomarkers for ovarian cancer detection and therapy

“…Deregulated claudin expression has been observed in gynecological cancers, such as cervical and endometrial cancers, as well as in premalignant lesions. [40][41][42] Claudin-3 and -4 were found to be overexpressed in EOC. 43,44 High expression of claudin-7 and -10 has also been observed in ovarian cancer, while claudin-3 expression was found to be associated with shorter survival in EOC.…”

The Effect of Commonly Used Excipients on the Epithelial Integrity of Human Cervicovaginal Tissue

“…Previous studies using kidney cell cultures suggested that paracellular permeability to electrical currents and non-charged solutes may be regulated by different sets of tight junctional proteins. [39][40][41][42][43] If this is the case, given that multiple types of tight junctional proteins are expressed in human cervicovaginal mucosa, 9,[44][45][46] it is possible that EDTA treatment affected certain tight junction proteins that control small-molecule movement, but it did not affect those that control electrical current flux. Such a change in the organization of tight junction, in our opinion, is not comparable to the physical breaches that facilitate HIV-1 entry into the submucosal compartment, [47][48][49] due to the difference in size and the entry mechanism between HIV-1 and mannitol.…”