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Acquisition of tumorigenic potential and enhancement of angiogenesis in pulmonary stem/progenitor cells through Oct-4 hyperexpression
Cancer stem cells, also known as cancer initiating cells (CICs), are considered to be responsible for tumor growth and chemoresistance. Different hypotheses have been proposed to explain the origin of CICs, including mutations in adult stem/progenitor cells or the acquisition of stem-like characteri...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4924688/ https://www.ncbi.nlm.nih.gov/pubmed/26871601 http://dx.doi.org/10.18632/oncotarget.7285 |
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author | Gu, Sing-Yi Ho, Choa-Chi Huang, Yung-Kang Chen, Huei-Wen Wang, Yu-Chi Kuo, Chia-Yu Teng, Shu-Chun Fu, Wen-Mei Yang, Pan-Chyr Wu, Cheng-Wen Peng, Fu-Chuo Ling, Thai-Yen |
author_facet | Gu, Sing-Yi Ho, Choa-Chi Huang, Yung-Kang Chen, Huei-Wen Wang, Yu-Chi Kuo, Chia-Yu Teng, Shu-Chun Fu, Wen-Mei Yang, Pan-Chyr Wu, Cheng-Wen Peng, Fu-Chuo Ling, Thai-Yen |
author_sort | Gu, Sing-Yi |
collection | PubMed |
description | Cancer stem cells, also known as cancer initiating cells (CICs), are considered to be responsible for tumor growth and chemoresistance. Different hypotheses have been proposed to explain the origin of CICs, including mutations in adult stem/progenitor cells or the acquisition of stem-like characteristics in differentiated cells; however, studies have yielded conflicting identification for CICs and have little information for the origin to generate CICs. Part of the difficulty in identifying CICs may stem from the fact that the CICs studied have been largely derived from cancer cell lines or well-developed tumors. In previous studies, we have reported the enrichment of mouse pulmonary stem/progenitor cells (mPSCs) by using serum-free primary selection culture followed by FACS isolation using the coxsackievirus/adenovirus receptor (CAR) as the positive selection marker. Here, we demonstrated that overexpression of the pluripotent transcription factor Oct-4 is sufficient to induce CAR(+)/mPSCs transformation, which we name CAR(+)/mPSCs(Oct-4_hi). These transformed cells possess cancer initiating and chemoresistance potential, as well as exhibiting remarkable expression of certain proangiogenic factors, including angiopoietins (ANGs) and VEGF, and enhanced angiogenic potential. Moreover, CAR(+)/mPSCs(Oct-4_hi) actively participated in tumor blood vessel formation and triggered a novel angiogenic mechanism, the angiopoietins/Tie2 signaling pathway. These study provide critical evidence supporting the possible origin to generate CICs, and help elucidate the pathways responsible for CICs-mediated blood vessel formation. |
format | Online Article Text |
id | pubmed-4924688 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-49246882016-07-13 Acquisition of tumorigenic potential and enhancement of angiogenesis in pulmonary stem/progenitor cells through Oct-4 hyperexpression Gu, Sing-Yi Ho, Choa-Chi Huang, Yung-Kang Chen, Huei-Wen Wang, Yu-Chi Kuo, Chia-Yu Teng, Shu-Chun Fu, Wen-Mei Yang, Pan-Chyr Wu, Cheng-Wen Peng, Fu-Chuo Ling, Thai-Yen Oncotarget Research Paper Cancer stem cells, also known as cancer initiating cells (CICs), are considered to be responsible for tumor growth and chemoresistance. Different hypotheses have been proposed to explain the origin of CICs, including mutations in adult stem/progenitor cells or the acquisition of stem-like characteristics in differentiated cells; however, studies have yielded conflicting identification for CICs and have little information for the origin to generate CICs. Part of the difficulty in identifying CICs may stem from the fact that the CICs studied have been largely derived from cancer cell lines or well-developed tumors. In previous studies, we have reported the enrichment of mouse pulmonary stem/progenitor cells (mPSCs) by using serum-free primary selection culture followed by FACS isolation using the coxsackievirus/adenovirus receptor (CAR) as the positive selection marker. Here, we demonstrated that overexpression of the pluripotent transcription factor Oct-4 is sufficient to induce CAR(+)/mPSCs transformation, which we name CAR(+)/mPSCs(Oct-4_hi). These transformed cells possess cancer initiating and chemoresistance potential, as well as exhibiting remarkable expression of certain proangiogenic factors, including angiopoietins (ANGs) and VEGF, and enhanced angiogenic potential. Moreover, CAR(+)/mPSCs(Oct-4_hi) actively participated in tumor blood vessel formation and triggered a novel angiogenic mechanism, the angiopoietins/Tie2 signaling pathway. These study provide critical evidence supporting the possible origin to generate CICs, and help elucidate the pathways responsible for CICs-mediated blood vessel formation. Impact Journals LLC 2016-02-09 /pmc/articles/PMC4924688/ /pubmed/26871601 http://dx.doi.org/10.18632/oncotarget.7285 Text en Copyright: © 2016 Gu 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 Gu, Sing-Yi Ho, Choa-Chi Huang, Yung-Kang Chen, Huei-Wen Wang, Yu-Chi Kuo, Chia-Yu Teng, Shu-Chun Fu, Wen-Mei Yang, Pan-Chyr Wu, Cheng-Wen Peng, Fu-Chuo Ling, Thai-Yen Acquisition of tumorigenic potential and enhancement of angiogenesis in pulmonary stem/progenitor cells through Oct-4 hyperexpression |
title | Acquisition of tumorigenic potential and enhancement of angiogenesis in pulmonary stem/progenitor cells through Oct-4 hyperexpression |
title_full | Acquisition of tumorigenic potential and enhancement of angiogenesis in pulmonary stem/progenitor cells through Oct-4 hyperexpression |
title_fullStr | Acquisition of tumorigenic potential and enhancement of angiogenesis in pulmonary stem/progenitor cells through Oct-4 hyperexpression |
title_full_unstemmed | Acquisition of tumorigenic potential and enhancement of angiogenesis in pulmonary stem/progenitor cells through Oct-4 hyperexpression |
title_short | Acquisition of tumorigenic potential and enhancement of angiogenesis in pulmonary stem/progenitor cells through Oct-4 hyperexpression |
title_sort | acquisition of tumorigenic potential and enhancement of angiogenesis in pulmonary stem/progenitor cells through oct-4 hyperexpression |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4924688/ https://www.ncbi.nlm.nih.gov/pubmed/26871601 http://dx.doi.org/10.18632/oncotarget.7285 |
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