Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
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
_version_ 1782439902403624960
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
work_keys_str_mv AT gusingyi acquisitionoftumorigenicpotentialandenhancementofangiogenesisinpulmonarystemprogenitorcellsthroughoct4hyperexpression
AT hochoachi acquisitionoftumorigenicpotentialandenhancementofangiogenesisinpulmonarystemprogenitorcellsthroughoct4hyperexpression
AT huangyungkang acquisitionoftumorigenicpotentialandenhancementofangiogenesisinpulmonarystemprogenitorcellsthroughoct4hyperexpression
AT chenhueiwen acquisitionoftumorigenicpotentialandenhancementofangiogenesisinpulmonarystemprogenitorcellsthroughoct4hyperexpression
AT wangyuchi acquisitionoftumorigenicpotentialandenhancementofangiogenesisinpulmonarystemprogenitorcellsthroughoct4hyperexpression
AT kuochiayu acquisitionoftumorigenicpotentialandenhancementofangiogenesisinpulmonarystemprogenitorcellsthroughoct4hyperexpression
AT tengshuchun acquisitionoftumorigenicpotentialandenhancementofangiogenesisinpulmonarystemprogenitorcellsthroughoct4hyperexpression
AT fuwenmei acquisitionoftumorigenicpotentialandenhancementofangiogenesisinpulmonarystemprogenitorcellsthroughoct4hyperexpression
AT yangpanchyr acquisitionoftumorigenicpotentialandenhancementofangiogenesisinpulmonarystemprogenitorcellsthroughoct4hyperexpression
AT wuchengwen acquisitionoftumorigenicpotentialandenhancementofangiogenesisinpulmonarystemprogenitorcellsthroughoct4hyperexpression
AT pengfuchuo acquisitionoftumorigenicpotentialandenhancementofangiogenesisinpulmonarystemprogenitorcellsthroughoct4hyperexpression
AT lingthaiyen acquisitionoftumorigenicpotentialandenhancementofangiogenesisinpulmonarystemprogenitorcellsthroughoct4hyperexpression