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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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.
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