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PTCH1 (+/−) Dermal Fibroblasts Isolated from Healthy Skin of Gorlin Syndrome Patients Exhibit Features of Carcinoma Associated Fibroblasts
Gorlin's or nevoid basal cell carcinoma syndrome (NBCCS) causes predisposition to basal cell carcinoma (BCC), the commonest cancer in adult human. Mutations in the tumor suppressor gene PTCH1 are responsible for this autosomal dominant syndrome. In NBCCS patients, as in the general population,...
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2009
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2654107/ https://www.ncbi.nlm.nih.gov/pubmed/19287498 http://dx.doi.org/10.1371/journal.pone.0004818 |
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author | Valin, Alexandre Barnay-Verdier, Stéphanie Robert, Thomas Ripoche, Hugues Brellier, Florence Chevallier-Lagente, Odile Avril, Marie-Françoise Magnaldo, Thierry |
author_facet | Valin, Alexandre Barnay-Verdier, Stéphanie Robert, Thomas Ripoche, Hugues Brellier, Florence Chevallier-Lagente, Odile Avril, Marie-Françoise Magnaldo, Thierry |
author_sort | Valin, Alexandre |
collection | PubMed |
description | Gorlin's or nevoid basal cell carcinoma syndrome (NBCCS) causes predisposition to basal cell carcinoma (BCC), the commonest cancer in adult human. Mutations in the tumor suppressor gene PTCH1 are responsible for this autosomal dominant syndrome. In NBCCS patients, as in the general population, ultraviolet exposure is a major risk factor for BCC development. However these patients also develop BCCs in sun-protected areas of the skin, suggesting the existence of other mechanisms for BCC predisposition in NBCCS patients. As increasing evidence supports the idea that the stroma influences carcinoma development, we hypothesized that NBCCS fibroblasts could facilitate BCC occurence of the patients. WT (n = 3) and NBCCS fibroblasts bearing either nonsense (n = 3) or missense (n = 3) PTCH1 mutations were cultured in dermal equivalents made of a collagen matrix and their transcriptomes were compared by whole genome microarray analyses. Strikingly, NBCCS fibroblasts over-expressed mRNAs encoding pro-tumoral factors such as Matrix Metalloproteinases 1 and 3 and tenascin C. They also over-expressed mRNA of pro-proliferative diffusible factors such as fibroblast growth factor 7 and the stromal cell-derived factor 1 alpha, known for its expression in carcinoma associated fibroblasts. These data indicate that the PTCH1(+/−) genotype of healthy NBCCS fibroblasts results in phenotypic traits highly reminiscent of those of BCC associated fibroblasts, a clue to the yet mysterious proneness to non photo-exposed BCCs in NBCCS patients. |
format | Text |
id | pubmed-2654107 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-26541072009-03-16 PTCH1 (+/−) Dermal Fibroblasts Isolated from Healthy Skin of Gorlin Syndrome Patients Exhibit Features of Carcinoma Associated Fibroblasts Valin, Alexandre Barnay-Verdier, Stéphanie Robert, Thomas Ripoche, Hugues Brellier, Florence Chevallier-Lagente, Odile Avril, Marie-Françoise Magnaldo, Thierry PLoS One Research Article Gorlin's or nevoid basal cell carcinoma syndrome (NBCCS) causes predisposition to basal cell carcinoma (BCC), the commonest cancer in adult human. Mutations in the tumor suppressor gene PTCH1 are responsible for this autosomal dominant syndrome. In NBCCS patients, as in the general population, ultraviolet exposure is a major risk factor for BCC development. However these patients also develop BCCs in sun-protected areas of the skin, suggesting the existence of other mechanisms for BCC predisposition in NBCCS patients. As increasing evidence supports the idea that the stroma influences carcinoma development, we hypothesized that NBCCS fibroblasts could facilitate BCC occurence of the patients. WT (n = 3) and NBCCS fibroblasts bearing either nonsense (n = 3) or missense (n = 3) PTCH1 mutations were cultured in dermal equivalents made of a collagen matrix and their transcriptomes were compared by whole genome microarray analyses. Strikingly, NBCCS fibroblasts over-expressed mRNAs encoding pro-tumoral factors such as Matrix Metalloproteinases 1 and 3 and tenascin C. They also over-expressed mRNA of pro-proliferative diffusible factors such as fibroblast growth factor 7 and the stromal cell-derived factor 1 alpha, known for its expression in carcinoma associated fibroblasts. These data indicate that the PTCH1(+/−) genotype of healthy NBCCS fibroblasts results in phenotypic traits highly reminiscent of those of BCC associated fibroblasts, a clue to the yet mysterious proneness to non photo-exposed BCCs in NBCCS patients. Public Library of Science 2009-03-16 /pmc/articles/PMC2654107/ /pubmed/19287498 http://dx.doi.org/10.1371/journal.pone.0004818 Text en Valin et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Valin, Alexandre Barnay-Verdier, Stéphanie Robert, Thomas Ripoche, Hugues Brellier, Florence Chevallier-Lagente, Odile Avril, Marie-Françoise Magnaldo, Thierry PTCH1 (+/−) Dermal Fibroblasts Isolated from Healthy Skin of Gorlin Syndrome Patients Exhibit Features of Carcinoma Associated Fibroblasts |
title |
PTCH1
(+/−) Dermal Fibroblasts Isolated from Healthy Skin of Gorlin Syndrome Patients Exhibit Features of Carcinoma Associated Fibroblasts |
title_full |
PTCH1
(+/−) Dermal Fibroblasts Isolated from Healthy Skin of Gorlin Syndrome Patients Exhibit Features of Carcinoma Associated Fibroblasts |
title_fullStr |
PTCH1
(+/−) Dermal Fibroblasts Isolated from Healthy Skin of Gorlin Syndrome Patients Exhibit Features of Carcinoma Associated Fibroblasts |
title_full_unstemmed |
PTCH1
(+/−) Dermal Fibroblasts Isolated from Healthy Skin of Gorlin Syndrome Patients Exhibit Features of Carcinoma Associated Fibroblasts |
title_short |
PTCH1
(+/−) Dermal Fibroblasts Isolated from Healthy Skin of Gorlin Syndrome Patients Exhibit Features of Carcinoma Associated Fibroblasts |
title_sort | ptch1
(+/−) dermal fibroblasts isolated from healthy skin of gorlin syndrome patients exhibit features of carcinoma associated fibroblasts |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2654107/ https://www.ncbi.nlm.nih.gov/pubmed/19287498 http://dx.doi.org/10.1371/journal.pone.0004818 |
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