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Converting melanoma-associated fibroblasts into a tumor-suppressive phenotype by increasing intracellular Notch1 pathway activity
Cancer-associated fibroblasts (CAFs) play a crucial role in cancer progression, drug resistance and tumor recurrence. We have recently shown that the Notch pathway determines the tumor-regulatory role of experimentally created ‘CAFs’. Here, we examined the status of Notch signaling in human melanoma...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7951899/ https://www.ncbi.nlm.nih.gov/pubmed/33705467 http://dx.doi.org/10.1371/journal.pone.0248260 |
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author | Shao, Hongwei Moller, Mecker Cai, Long Prokupets, Rochelle Yang, Cuixia Costa, Connor Yu, Kerstin Le, Nga Liu, Zhao-Jun |
author_facet | Shao, Hongwei Moller, Mecker Cai, Long Prokupets, Rochelle Yang, Cuixia Costa, Connor Yu, Kerstin Le, Nga Liu, Zhao-Jun |
author_sort | Shao, Hongwei |
collection | PubMed |
description | Cancer-associated fibroblasts (CAFs) play a crucial role in cancer progression, drug resistance and tumor recurrence. We have recently shown that the Notch pathway determines the tumor-regulatory role of experimentally created ‘CAFs’. Here, we examined the status of Notch signaling in human melanoma-associated fibroblasts (MAFs) versus their normal counterparts and tested whether manipulation of the Notch pathway activity in MAFs alters their tumor-regulatory function. Using tissue microarrays, we found that MAFs exhibit decreased Notch pathway activity compared with normal fibroblasts in adjacent and non-adjacent skin. Consistently, MAFs isolated from human metastatic melanoma exhibited lower Notch activity than did normal human fibroblasts, demonstrating that Notch pathway activity is low in MAFs. We then investigated the effect of increasing Notch pathway activity in MAF on melanoma growth in co-cultures and in a mouse co-graft model. We found that activation of the Notch pathway in MAFs significantly restricted melanoma cell growth in vitro and suppressed melanoma skin growth and tumor angiogenesis in vivo. Our study demonstrates that the Notch signaling is inhibited in MAFs. Increase of Notch pathway activity can confer tumor-suppressive function on MAFs. Thus, targeting melanoma by activating Notch signaling in MAF may represent a novel therapeutic approach. |
format | Online Article Text |
id | pubmed-7951899 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-79518992021-03-22 Converting melanoma-associated fibroblasts into a tumor-suppressive phenotype by increasing intracellular Notch1 pathway activity Shao, Hongwei Moller, Mecker Cai, Long Prokupets, Rochelle Yang, Cuixia Costa, Connor Yu, Kerstin Le, Nga Liu, Zhao-Jun PLoS One Research Article Cancer-associated fibroblasts (CAFs) play a crucial role in cancer progression, drug resistance and tumor recurrence. We have recently shown that the Notch pathway determines the tumor-regulatory role of experimentally created ‘CAFs’. Here, we examined the status of Notch signaling in human melanoma-associated fibroblasts (MAFs) versus their normal counterparts and tested whether manipulation of the Notch pathway activity in MAFs alters their tumor-regulatory function. Using tissue microarrays, we found that MAFs exhibit decreased Notch pathway activity compared with normal fibroblasts in adjacent and non-adjacent skin. Consistently, MAFs isolated from human metastatic melanoma exhibited lower Notch activity than did normal human fibroblasts, demonstrating that Notch pathway activity is low in MAFs. We then investigated the effect of increasing Notch pathway activity in MAF on melanoma growth in co-cultures and in a mouse co-graft model. We found that activation of the Notch pathway in MAFs significantly restricted melanoma cell growth in vitro and suppressed melanoma skin growth and tumor angiogenesis in vivo. Our study demonstrates that the Notch signaling is inhibited in MAFs. Increase of Notch pathway activity can confer tumor-suppressive function on MAFs. Thus, targeting melanoma by activating Notch signaling in MAF may represent a novel therapeutic approach. Public Library of Science 2021-03-11 /pmc/articles/PMC7951899/ /pubmed/33705467 http://dx.doi.org/10.1371/journal.pone.0248260 Text en © 2021 Shao 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 (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Shao, Hongwei Moller, Mecker Cai, Long Prokupets, Rochelle Yang, Cuixia Costa, Connor Yu, Kerstin Le, Nga Liu, Zhao-Jun Converting melanoma-associated fibroblasts into a tumor-suppressive phenotype by increasing intracellular Notch1 pathway activity |
title | Converting melanoma-associated fibroblasts into a tumor-suppressive phenotype by increasing intracellular Notch1 pathway activity |
title_full | Converting melanoma-associated fibroblasts into a tumor-suppressive phenotype by increasing intracellular Notch1 pathway activity |
title_fullStr | Converting melanoma-associated fibroblasts into a tumor-suppressive phenotype by increasing intracellular Notch1 pathway activity |
title_full_unstemmed | Converting melanoma-associated fibroblasts into a tumor-suppressive phenotype by increasing intracellular Notch1 pathway activity |
title_short | Converting melanoma-associated fibroblasts into a tumor-suppressive phenotype by increasing intracellular Notch1 pathway activity |
title_sort | converting melanoma-associated fibroblasts into a tumor-suppressive phenotype by increasing intracellular notch1 pathway activity |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7951899/ https://www.ncbi.nlm.nih.gov/pubmed/33705467 http://dx.doi.org/10.1371/journal.pone.0248260 |
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