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Tumour PDGF-BB expr...
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Hosaka, KayokoKarolinska Institutet
(author)
Tumour PDGF-BB expression levels determine dual effects of anti-PDGF drugs on vascular remodelling and metastasis
- Article/chapterEnglish2013
Publisher, publication year, extent ...
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2013-07-08
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Nature Publishing Group: Nature Communications,2013
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:liu-97672
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https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-97672URI
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https://doi.org/10.1038/ncomms3129DOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:127291200URI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Funding Agencies|Swedish Research Council||Swedish Cancer Foundation||Karolinska Institute Foundation||Karolinska Institute||Tianjin Natural Science Foundation (CMM-Tianjin)|09ZCZDSF04400|Torsten Soderbergs foundation||European Union Integrated Project of Metoxia|222741|European Research Council (ERC)|250021|
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Anti-platelet-derived growth factor (PDGF) drugs are routinely used in front-line therapy for the treatment of various cancers, but the molecular mechanism underlying their dose-dependent impact on vascular remodelling remains poorly understood. Here we show that anti-PDGF drugs significantly inhibit tumour growth and metastasis in high PDGF-BB-producing tumours by preventing pericyte loss and vascular permeability, whereas they promote tumour cell dissemination and metastasis in PDGF-BB-low-producing or PDGF-BB-negative tumours by ablating pericytes from tumour vessels. We show that this opposing effect is due to PDGF-beta signalling in pericytes. Persistent exposure of pericytes to PDGF-BB markedly downregulates PDGF-beta and inactivation of the PDGF-beta signalling decreases integrin alpha 1 beta 1 levels, which impairs pericyte adhesion to extracellular matrix components in blood vessels. Our data suggest that tumour PDGF-BB levels may serve as a biomarker for selection of tumour-bearing hosts for anti-PDGF therapy and unsupervised use of anti-PDGF drugs could potentially promote tumour invasion and metastasis.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
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Yang, YunlongKarolinska Institutet
(author)
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Seki, TakahiroKarolinska Institutet
(author)
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Nakamura, MasakiKarolinska Institutet
(author)
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Andersson, PatrikKarolinska Institutet
(author)
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Rouhi, PegahKarolinska Institute, Sweden
(author)
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Yang, XiaojuanKarolinska Institute, Sweden
(author)
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Jensen, LasseKarolinska Institutet,Linköpings universitet,Avdelningen för kardiovaskulär medicin,Hälsouniversitetet,Karolinska Institute, Sweden(Swepub:liu)larje86
(author)
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Lim, SharonKarolinska Institutet
(author)
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Feng, NinghanKarolinska Institute, Sweden
(author)
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Xue, YuanKarolinska Institute, Sweden
(author)
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Li, XuriSun Yat Sen University, Peoples R China
(author)
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Larsson, OlaKarolinska Institutet
(author)
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Ohhashi, ToshioShinshu University, Japan
(author)
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Cao, YihaiLinköpings universitet,Avdelningen för kardiovaskulär medicin,Hälsouniversitetet,Karolinska Institute, Sweden(Swepub:liu)yihca64
(author)
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Karolinska InstitutetKarolinska Institute, Sweden
(creator_code:org_t)
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In:Nature Communications: Nature Publishing Group: Nature Communications4:21292041-1723
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- By the author/editor
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Hosaka, Kayoko
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Yang, Yunlong
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Seki, Takahiro
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Nakamura, Masaki
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Andersson, Patri ...
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Rouhi, Pegah
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Yang, Xiaojuan
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Jensen, Lasse
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Lim, Sharon
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Feng, Ninghan
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Xue, Yuan
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Li, Xuri
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Larsson, Ola
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Ohhashi, Toshio
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Cao, Yihai
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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Nature Communica ...
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Linköping University
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Karolinska Institutet