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Identification of CD146 as a marker enriched for tumor-propagating capacity reveals targetable pathways in primary human sarcoma
Tumor-propagating cells (TPCs) are believed to drive cancer initiation, progression and recurrence. These cells are characterized by enhanced tumorigenicity and self-renewal. The ability to identify such cells in primary human sarcomas relies on the dye exclusion ability of tumor side population (SP...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4741895/ https://www.ncbi.nlm.nih.gov/pubmed/26517673 |
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author | Wei, Qingxia Tang, Yuning J. Voisin, Veronique Sato, Shingo Hirata, Makoto Whetstone, Heather Han, Ilkyu Ailles, Laurie Bader, Gary D. Wunder, Jay Alman, Benjamin A. |
author_facet | Wei, Qingxia Tang, Yuning J. Voisin, Veronique Sato, Shingo Hirata, Makoto Whetstone, Heather Han, Ilkyu Ailles, Laurie Bader, Gary D. Wunder, Jay Alman, Benjamin A. |
author_sort | Wei, Qingxia |
collection | PubMed |
description | Tumor-propagating cells (TPCs) are believed to drive cancer initiation, progression and recurrence. These cells are characterized by enhanced tumorigenicity and self-renewal. The ability to identify such cells in primary human sarcomas relies on the dye exclusion ability of tumor side population (SP) cells. Here, we performed a high-throughput cell surface antigen screen and found that CD146 is enriched in the SP population. In vivo serial transplantation assays showed that CD146(+) cells are highly tumorigenic, capable of self-renewal and thus enriches for the TPC population. In addition, depletion of SP cells from the CD146(+) population show that CD146(+) cells and SP cells are a distinct and overlapping TPC populations. Gene expression profiling of CD146(+) and SP cells revealed multiple pathways commonly upregulated in both of these populations. Inhibition of one of these upregulated pathways, Notch signaling, significantly reduced tumor growth and self-renewal. Our data demonstrate that CD146 is an effective cell surface marker for enriching TPCs in primary human sarcomas. Targeting differentially activated pathways in TPCs may provide new therapeutic strategies for treating sarcoma. |
format | Online Article Text |
id | pubmed-4741895 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-47418952016-03-23 Identification of CD146 as a marker enriched for tumor-propagating capacity reveals targetable pathways in primary human sarcoma Wei, Qingxia Tang, Yuning J. Voisin, Veronique Sato, Shingo Hirata, Makoto Whetstone, Heather Han, Ilkyu Ailles, Laurie Bader, Gary D. Wunder, Jay Alman, Benjamin A. Oncotarget Research Paper Tumor-propagating cells (TPCs) are believed to drive cancer initiation, progression and recurrence. These cells are characterized by enhanced tumorigenicity and self-renewal. The ability to identify such cells in primary human sarcomas relies on the dye exclusion ability of tumor side population (SP) cells. Here, we performed a high-throughput cell surface antigen screen and found that CD146 is enriched in the SP population. In vivo serial transplantation assays showed that CD146(+) cells are highly tumorigenic, capable of self-renewal and thus enriches for the TPC population. In addition, depletion of SP cells from the CD146(+) population show that CD146(+) cells and SP cells are a distinct and overlapping TPC populations. Gene expression profiling of CD146(+) and SP cells revealed multiple pathways commonly upregulated in both of these populations. Inhibition of one of these upregulated pathways, Notch signaling, significantly reduced tumor growth and self-renewal. Our data demonstrate that CD146 is an effective cell surface marker for enriching TPCs in primary human sarcomas. Targeting differentially activated pathways in TPCs may provide new therapeutic strategies for treating sarcoma. Impact Journals LLC 2015-10-26 /pmc/articles/PMC4741895/ /pubmed/26517673 Text en Copyright: © 2015 Wei et al. http://creativecommons.org/licenses/by/2.5/ 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 credited. |
spellingShingle | Research Paper Wei, Qingxia Tang, Yuning J. Voisin, Veronique Sato, Shingo Hirata, Makoto Whetstone, Heather Han, Ilkyu Ailles, Laurie Bader, Gary D. Wunder, Jay Alman, Benjamin A. Identification of CD146 as a marker enriched for tumor-propagating capacity reveals targetable pathways in primary human sarcoma |
title | Identification of CD146 as a marker enriched for tumor-propagating capacity reveals targetable pathways in primary human sarcoma |
title_full | Identification of CD146 as a marker enriched for tumor-propagating capacity reveals targetable pathways in primary human sarcoma |
title_fullStr | Identification of CD146 as a marker enriched for tumor-propagating capacity reveals targetable pathways in primary human sarcoma |
title_full_unstemmed | Identification of CD146 as a marker enriched for tumor-propagating capacity reveals targetable pathways in primary human sarcoma |
title_short | Identification of CD146 as a marker enriched for tumor-propagating capacity reveals targetable pathways in primary human sarcoma |
title_sort | identification of cd146 as a marker enriched for tumor-propagating capacity reveals targetable pathways in primary human sarcoma |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4741895/ https://www.ncbi.nlm.nih.gov/pubmed/26517673 |
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