Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4741895/
https://www.ncbi.nlm.nih.gov/pubmed/26517673
_version_ 1782414094558560256
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
work_keys_str_mv AT weiqingxia identificationofcd146asamarkerenrichedfortumorpropagatingcapacityrevealstargetablepathwaysinprimaryhumansarcoma
AT tangyuningj identificationofcd146asamarkerenrichedfortumorpropagatingcapacityrevealstargetablepathwaysinprimaryhumansarcoma
AT voisinveronique identificationofcd146asamarkerenrichedfortumorpropagatingcapacityrevealstargetablepathwaysinprimaryhumansarcoma
AT satoshingo identificationofcd146asamarkerenrichedfortumorpropagatingcapacityrevealstargetablepathwaysinprimaryhumansarcoma
AT hiratamakoto identificationofcd146asamarkerenrichedfortumorpropagatingcapacityrevealstargetablepathwaysinprimaryhumansarcoma
AT whetstoneheather identificationofcd146asamarkerenrichedfortumorpropagatingcapacityrevealstargetablepathwaysinprimaryhumansarcoma
AT hanilkyu identificationofcd146asamarkerenrichedfortumorpropagatingcapacityrevealstargetablepathwaysinprimaryhumansarcoma
AT ailleslaurie identificationofcd146asamarkerenrichedfortumorpropagatingcapacityrevealstargetablepathwaysinprimaryhumansarcoma
AT badergaryd identificationofcd146asamarkerenrichedfortumorpropagatingcapacityrevealstargetablepathwaysinprimaryhumansarcoma
AT wunderjay identificationofcd146asamarkerenrichedfortumorpropagatingcapacityrevealstargetablepathwaysinprimaryhumansarcoma
AT almanbenjamina identificationofcd146asamarkerenrichedfortumorpropagatingcapacityrevealstargetablepathwaysinprimaryhumansarcoma