Cargando…
Cancer cell-secreted IGF2 instigates fibroblasts and bone marrow-derived vascular progenitor cells to promote cancer progression
Local interactions between cancer cells and stroma can produce systemic effects on distant organs to govern cancer progression. Here we show that IGF2 secreted by inhibitor of differentiation (Id1)-overexpressing oesophageal cancer cells instigates VEGFR1-positive bone marrow cells in the tumour mac...
Autores principales: | , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5309924/ https://www.ncbi.nlm.nih.gov/pubmed/28186102 http://dx.doi.org/10.1038/ncomms14399 |
_version_ | 1782507793742299136 |
---|---|
author | Xu, Wen Wen Li, Bin Guan, Xin Yuan Chung, Sookja K. Wang, Yang Yip, Yim Ling Law, Simon Y. K. Chan, Kin Tak Lee, Nikki P. Y. Chan, Kwok Wah Xu, Li Yan Li, En Min Tsao, Sai Wah He, Qing-Yu Cheung, Annie L. M. |
author_facet | Xu, Wen Wen Li, Bin Guan, Xin Yuan Chung, Sookja K. Wang, Yang Yip, Yim Ling Law, Simon Y. K. Chan, Kin Tak Lee, Nikki P. Y. Chan, Kwok Wah Xu, Li Yan Li, En Min Tsao, Sai Wah He, Qing-Yu Cheung, Annie L. M. |
author_sort | Xu, Wen Wen |
collection | PubMed |
description | Local interactions between cancer cells and stroma can produce systemic effects on distant organs to govern cancer progression. Here we show that IGF2 secreted by inhibitor of differentiation (Id1)-overexpressing oesophageal cancer cells instigates VEGFR1-positive bone marrow cells in the tumour macroenvironment to form pre-metastatic niches at distant sites by increasing VEGF secretion from cancer-associated fibroblasts. Cancer cells are then attracted to the metastatic site via the CXCL5/CXCR2 axis. Bone marrow cells transplanted from nude mice bearing Id1-overexpressing oesophageal tumours enhance tumour growth and metastasis in recipient mice, whereas systemic administration of VEGFR1 antibody abrogates these effects. Mechanistically, IGF2 regulates VEGF in fibroblasts via miR-29c in a p53-dependent manner. Analysis of patient serum samples showed that concurrent elevation of IGF2 and VEGF levels may serve as a prognostic biomarker for oesophageal cancer. These findings suggest that the Id1/IGF2/VEGF/VEGFR1 cascade plays a critical role in tumour-driven pathophysiological processes underlying cancer progression. |
format | Online Article Text |
id | pubmed-5309924 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-53099242017-02-27 Cancer cell-secreted IGF2 instigates fibroblasts and bone marrow-derived vascular progenitor cells to promote cancer progression Xu, Wen Wen Li, Bin Guan, Xin Yuan Chung, Sookja K. Wang, Yang Yip, Yim Ling Law, Simon Y. K. Chan, Kin Tak Lee, Nikki P. Y. Chan, Kwok Wah Xu, Li Yan Li, En Min Tsao, Sai Wah He, Qing-Yu Cheung, Annie L. M. Nat Commun Article Local interactions between cancer cells and stroma can produce systemic effects on distant organs to govern cancer progression. Here we show that IGF2 secreted by inhibitor of differentiation (Id1)-overexpressing oesophageal cancer cells instigates VEGFR1-positive bone marrow cells in the tumour macroenvironment to form pre-metastatic niches at distant sites by increasing VEGF secretion from cancer-associated fibroblasts. Cancer cells are then attracted to the metastatic site via the CXCL5/CXCR2 axis. Bone marrow cells transplanted from nude mice bearing Id1-overexpressing oesophageal tumours enhance tumour growth and metastasis in recipient mice, whereas systemic administration of VEGFR1 antibody abrogates these effects. Mechanistically, IGF2 regulates VEGF in fibroblasts via miR-29c in a p53-dependent manner. Analysis of patient serum samples showed that concurrent elevation of IGF2 and VEGF levels may serve as a prognostic biomarker for oesophageal cancer. These findings suggest that the Id1/IGF2/VEGF/VEGFR1 cascade plays a critical role in tumour-driven pathophysiological processes underlying cancer progression. Nature Publishing Group 2017-02-10 /pmc/articles/PMC5309924/ /pubmed/28186102 http://dx.doi.org/10.1038/ncomms14399 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Xu, Wen Wen Li, Bin Guan, Xin Yuan Chung, Sookja K. Wang, Yang Yip, Yim Ling Law, Simon Y. K. Chan, Kin Tak Lee, Nikki P. Y. Chan, Kwok Wah Xu, Li Yan Li, En Min Tsao, Sai Wah He, Qing-Yu Cheung, Annie L. M. Cancer cell-secreted IGF2 instigates fibroblasts and bone marrow-derived vascular progenitor cells to promote cancer progression |
title | Cancer cell-secreted IGF2 instigates fibroblasts and bone marrow-derived vascular progenitor cells to promote cancer progression |
title_full | Cancer cell-secreted IGF2 instigates fibroblasts and bone marrow-derived vascular progenitor cells to promote cancer progression |
title_fullStr | Cancer cell-secreted IGF2 instigates fibroblasts and bone marrow-derived vascular progenitor cells to promote cancer progression |
title_full_unstemmed | Cancer cell-secreted IGF2 instigates fibroblasts and bone marrow-derived vascular progenitor cells to promote cancer progression |
title_short | Cancer cell-secreted IGF2 instigates fibroblasts and bone marrow-derived vascular progenitor cells to promote cancer progression |
title_sort | cancer cell-secreted igf2 instigates fibroblasts and bone marrow-derived vascular progenitor cells to promote cancer progression |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5309924/ https://www.ncbi.nlm.nih.gov/pubmed/28186102 http://dx.doi.org/10.1038/ncomms14399 |
work_keys_str_mv | AT xuwenwen cancercellsecretedigf2instigatesfibroblastsandbonemarrowderivedvascularprogenitorcellstopromotecancerprogression AT libin cancercellsecretedigf2instigatesfibroblastsandbonemarrowderivedvascularprogenitorcellstopromotecancerprogression AT guanxinyuan cancercellsecretedigf2instigatesfibroblastsandbonemarrowderivedvascularprogenitorcellstopromotecancerprogression AT chungsookjak cancercellsecretedigf2instigatesfibroblastsandbonemarrowderivedvascularprogenitorcellstopromotecancerprogression AT wangyang cancercellsecretedigf2instigatesfibroblastsandbonemarrowderivedvascularprogenitorcellstopromotecancerprogression AT yipyimling cancercellsecretedigf2instigatesfibroblastsandbonemarrowderivedvascularprogenitorcellstopromotecancerprogression AT lawsimonyk cancercellsecretedigf2instigatesfibroblastsandbonemarrowderivedvascularprogenitorcellstopromotecancerprogression AT chankintak cancercellsecretedigf2instigatesfibroblastsandbonemarrowderivedvascularprogenitorcellstopromotecancerprogression AT leenikkipy cancercellsecretedigf2instigatesfibroblastsandbonemarrowderivedvascularprogenitorcellstopromotecancerprogression AT chankwokwah cancercellsecretedigf2instigatesfibroblastsandbonemarrowderivedvascularprogenitorcellstopromotecancerprogression AT xuliyan cancercellsecretedigf2instigatesfibroblastsandbonemarrowderivedvascularprogenitorcellstopromotecancerprogression AT lienmin cancercellsecretedigf2instigatesfibroblastsandbonemarrowderivedvascularprogenitorcellstopromotecancerprogression AT tsaosaiwah cancercellsecretedigf2instigatesfibroblastsandbonemarrowderivedvascularprogenitorcellstopromotecancerprogression AT heqingyu cancercellsecretedigf2instigatesfibroblastsandbonemarrowderivedvascularprogenitorcellstopromotecancerprogression AT cheungannielm cancercellsecretedigf2instigatesfibroblastsandbonemarrowderivedvascularprogenitorcellstopromotecancerprogression |