The barrier function of organotypic non-melanoma skin cancer models

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F16%3A10328161" target="_blank" >RIV/00216208:11160/16:10328161 - isvavai.cz</a>

Výsledek na webu

<a href="http://www.sciencedirect.com/science/article/pii/S0168365916302516" target="_blank" >http://www.sciencedirect.com/science/article/pii/S0168365916302516</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.jconrel.2016.04.037" target="_blank" >10.1016/j.jconrel.2016.04.037</a>

Jazyk výsledku

angličtina

Název v původním jazyce

The barrier function of organotypic non-melanoma skin cancer models

Popis výsledku v původním jazyce

Non-melanoma skin cancer (NMSC) is the most frequent human cancer with continuously rising incidences worldwide. Herein, we investigated the molecular basis for the impaired skin barrier function of organotypic NMSC models. We unraveled disturbed epidermal differentiation by reflectance confocal microscopy and histopathological evaluation. While the presence of claudin-4 and occludin were distinctly reduced, zonula occludens protein-1 was more wide-spread, and claudin-1 was heterogeneously distributed within the NMSC models compared with normal reconstructed human skin. Moreover, the cancer altered stratum corneum lipid packing and profile with decreased cholesterol content, increased phospholipid amount, and altered ceramide subclasses. These alterations contributed to increased surface pH and to 1.5 to 2.6-fold enhanced caffeine permeability of the NMSC models. Three topical applications of ingenol mebutate gel (0.015%) caused abundant epidermal cell necrosis, decreased Ki-67 indices, and increased lactate dehydrogenase activity. Taken together, our study provides new biological insights into the microenvironment of organotypic NMSC models, improves the understanding of the disease model by revealing causes for impaired skin barrier function in NMSC models at the molecular level, and fosters human cell-based approaches in preclinical drug evaluation.

Název v anglickém jazyce

The barrier function of organotypic non-melanoma skin cancer models

Popis výsledku anglicky

Non-melanoma skin cancer (NMSC) is the most frequent human cancer with continuously rising incidences worldwide. Herein, we investigated the molecular basis for the impaired skin barrier function of organotypic NMSC models. We unraveled disturbed epidermal differentiation by reflectance confocal microscopy and histopathological evaluation. While the presence of claudin-4 and occludin were distinctly reduced, zonula occludens protein-1 was more wide-spread, and claudin-1 was heterogeneously distributed within the NMSC models compared with normal reconstructed human skin. Moreover, the cancer altered stratum corneum lipid packing and profile with decreased cholesterol content, increased phospholipid amount, and altered ceramide subclasses. These alterations contributed to increased surface pH and to 1.5 to 2.6-fold enhanced caffeine permeability of the NMSC models. Three topical applications of ingenol mebutate gel (0.015%) caused abundant epidermal cell necrosis, decreased Ki-67 indices, and increased lactate dehydrogenase activity. Taken together, our study provides new biological insights into the microenvironment of organotypic NMSC models, improves the understanding of the disease model by revealing causes for impaired skin barrier function in NMSC models at the molecular level, and fosters human cell-based approaches in preclinical drug evaluation.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

FR - Farmakologie a lékárnická chemie

OECD FORD obor

—

Projekt

<a href="/cs/project/GA13-23891S" target="_blank" >GA13-23891S: Modely lipidových membrán - nový nástroj pro studium patofyziologie kožních onemocnění na molekulární úrovni</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2016

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Controlled Release

ISSN

0168-3659

e-ISSN

—

Svazek periodika

233

Číslo periodika v rámci svazku

July

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

9

Strana od-do

10-18

Kód UT WoS článku

000378056400002

EID výsledku v databázi Scopus

2-s2.0-84968919491