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The Role of Dermal Fibroblasts in Nevoid Basal Cell Carcinoma Syndrome Patients: An Overview

Nevoid basal cell carcinoma syndrome (NBCCS), also named Gorlin syndrome, is a rare multisystem genetic disorder characterized by marked predisposition to basal cell carcinomas (BCCs), childhood medulloblastomas, maxillary keratocysts, celebral calcifications, in addition to various skeletal and sof...

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Autores principales: Bellei, Barbara, Caputo, Silvia, Carbone, Anna, Silipo, Vitaliano, Papaccio, Federica, Picardo, Mauro, Eibenschutz, Laura
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7037136/
https://www.ncbi.nlm.nih.gov/pubmed/31979112
http://dx.doi.org/10.3390/ijms21030720
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author Bellei, Barbara
Caputo, Silvia
Carbone, Anna
Silipo, Vitaliano
Papaccio, Federica
Picardo, Mauro
Eibenschutz, Laura
author_facet Bellei, Barbara
Caputo, Silvia
Carbone, Anna
Silipo, Vitaliano
Papaccio, Federica
Picardo, Mauro
Eibenschutz, Laura
author_sort Bellei, Barbara
collection PubMed
description Nevoid basal cell carcinoma syndrome (NBCCS), also named Gorlin syndrome, is a rare multisystem genetic disorder characterized by marked predisposition to basal cell carcinomas (BCCs), childhood medulloblastomas, maxillary keratocysts, celebral calcifications, in addition to various skeletal and soft tissue developmental abnormalities. Mutations in the tumor suppressor gene PATCHED1 (PTCH1) have been found to be associated in the majority of NBCCS cases. PATCH1 somatic mutations and loss of heterozygosity are also very frequent in sporadic BCCs. Unlike non-syndromic patients, NBCCS patients develop multiple BCCs in sun-protected skin area starting from early adulthood. Recent studies suggest that dermo/epidermal interaction could be implicated in BCC predisposition. According to this idea, NBCCS fibroblasts, sharing with keratinocytes the same PTCH1 germline mutation and consequent constitutive activation of the Hh pathway, display features of carcinoma-associated fibroblasts (CAF). This phenotypic traits include the overexpression of growth factors, specific microRNAs profile, modification of extracellular matrix and basement membrane composition, increased cytokines and pro-angiogenic factors secretion, and a complex alteration of the Wnt/β-catenin pathway. Here, we review studies about the involvement of dermal fibroblasts in BCC predisposition of Gorlin syndrome patients. Further, we matched the emerged NBCCS fibroblast profile to those of CAF to compare the impact of cell autonomous “pre-activated state” due to PTCH1 mutations to those of skin tumor stroma.
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spelling pubmed-70371362020-03-11 The Role of Dermal Fibroblasts in Nevoid Basal Cell Carcinoma Syndrome Patients: An Overview Bellei, Barbara Caputo, Silvia Carbone, Anna Silipo, Vitaliano Papaccio, Federica Picardo, Mauro Eibenschutz, Laura Int J Mol Sci Review Nevoid basal cell carcinoma syndrome (NBCCS), also named Gorlin syndrome, is a rare multisystem genetic disorder characterized by marked predisposition to basal cell carcinomas (BCCs), childhood medulloblastomas, maxillary keratocysts, celebral calcifications, in addition to various skeletal and soft tissue developmental abnormalities. Mutations in the tumor suppressor gene PATCHED1 (PTCH1) have been found to be associated in the majority of NBCCS cases. PATCH1 somatic mutations and loss of heterozygosity are also very frequent in sporadic BCCs. Unlike non-syndromic patients, NBCCS patients develop multiple BCCs in sun-protected skin area starting from early adulthood. Recent studies suggest that dermo/epidermal interaction could be implicated in BCC predisposition. According to this idea, NBCCS fibroblasts, sharing with keratinocytes the same PTCH1 germline mutation and consequent constitutive activation of the Hh pathway, display features of carcinoma-associated fibroblasts (CAF). This phenotypic traits include the overexpression of growth factors, specific microRNAs profile, modification of extracellular matrix and basement membrane composition, increased cytokines and pro-angiogenic factors secretion, and a complex alteration of the Wnt/β-catenin pathway. Here, we review studies about the involvement of dermal fibroblasts in BCC predisposition of Gorlin syndrome patients. Further, we matched the emerged NBCCS fibroblast profile to those of CAF to compare the impact of cell autonomous “pre-activated state” due to PTCH1 mutations to those of skin tumor stroma. MDPI 2020-01-22 /pmc/articles/PMC7037136/ /pubmed/31979112 http://dx.doi.org/10.3390/ijms21030720 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Bellei, Barbara
Caputo, Silvia
Carbone, Anna
Silipo, Vitaliano
Papaccio, Federica
Picardo, Mauro
Eibenschutz, Laura
The Role of Dermal Fibroblasts in Nevoid Basal Cell Carcinoma Syndrome Patients: An Overview
title The Role of Dermal Fibroblasts in Nevoid Basal Cell Carcinoma Syndrome Patients: An Overview
title_full The Role of Dermal Fibroblasts in Nevoid Basal Cell Carcinoma Syndrome Patients: An Overview
title_fullStr The Role of Dermal Fibroblasts in Nevoid Basal Cell Carcinoma Syndrome Patients: An Overview
title_full_unstemmed The Role of Dermal Fibroblasts in Nevoid Basal Cell Carcinoma Syndrome Patients: An Overview
title_short The Role of Dermal Fibroblasts in Nevoid Basal Cell Carcinoma Syndrome Patients: An Overview
title_sort role of dermal fibroblasts in nevoid basal cell carcinoma syndrome patients: an overview
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7037136/
https://www.ncbi.nlm.nih.gov/pubmed/31979112
http://dx.doi.org/10.3390/ijms21030720
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