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Collaborative inter...
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Cao, RenhaiKarolinska Institutet
(author)
Collaborative interplay between FGF-2 and VEGF-C promotes lymphangiogenesis and metastasis
- Article/chapterEnglish2012
Publisher, publication year, extent ...
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2012-09-11
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National Academy of Sciences,2012
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:liu-85089
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https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-85089URI
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https://doi.org/10.1073/pnas.1208324109DOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:125387598URI
Supplementary language notes
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Language:English
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Summary in:English
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Classification
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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 distinguished professor award||Torsten Soderbergs Foundation||ImClone Systems/EliLilly||European Union Integrated Project of Metoxia|222741|Nordea Foundation||European Research Council advanced Grant ANGIOFAT|250021|
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Interplay between various lymphangiogenic factors in promoting lymphangiogenesis and lymphatic metastasis remains poorly understood. Here we show that FGF-2 and VEGF-C, two lymphangiogenic factors, collaboratively promote angiogenesis and lymphangiogenesis in the tumor microenvironment, leading to widespread pulmonary and lymph-node metastases. Coimplantation of dual factors in the mouse cornea resulted in additive angiogenesis and lymphangiogenesis. At the molecular level, we showed that FGFR-1 expressed in lymphatic endothelial cells is a crucial receptor that mediates the FGF-2-induced lymphangiogenesis. Intriguingly, the VEGFR-3-mediated signaling was required for the lymphatic tip cell formation in both FGF-2- and VEGF-C-induced lymphangiogenesis. Consequently, a VEGFR-3-specific neutralizing antibody markedly inhibited FGF-2-induced lymphangiogenesis. Thus, the VEGFR-3-induced lymphatic endothelial cell tip cell formation is a prerequisite for FGF-2-stimulated lymphangiogenesis. In the tumor microenvironment, the reciprocal interplay between FGF-2 and VEGF-C collaboratively stimulated tumor growth, angiogenesis, intratumoral lymphangiogenesis, and metastasis. Thus, intervention and targeting of the FGF-2- and VEGF-C-induced angiogenic and lymphangiogenic synergism could be potentially important approaches for cancer therapy and prevention of metastasis.
Subject headings and genre
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neovascularization
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growth factors
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signaling interplay
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cancer spread
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antiangiogenic therapy
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SOCIAL SCIENCES
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SAMHÄLLSVETENSKAP
Added entries (persons, corporate bodies, meetings, titles ...)
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Ji, HongKarolinska Institutet
(author)
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Feng, NinghanDepartment of Microbiology, Tumor, and Cell Biology, Karolinska Institute, Stockholm, Sweden
(author)
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Zhang, YinKarolinska Institutet
(author)
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Yang, XiaojuanDepartment of Microbiology, Tumor, and Cell Biology, Karolinska Institute, Stockholm, Sweden
(author)
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Andersson, PatrikKarolinska Institutet
(author)
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Sun, YupingDepartment of Oncology, Jinan Central Hospital, Shandong University, Jinan, Shandong , People's Republic of China
(author)
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Tritsaris, KaterinaDepartment of Cellular and Molecular Medicine, Center for Healthy Aging Panum Institute, University of Copenhagen, Copenhagen, Denmark
(author)
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Jon Hansen, AnkerDepartment of Neuroscience and Pharmacology, Panum Institute, University of Copenhagen, Copenhagen, Denmark and Novo Nordisk A/S Måløv, Denmark
(author)
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Dissing, SteenDepartment of Cellular and Molecular Medicine, Center for Healthy Aging Panum Institute, University of Copenhagen, Copenhagen, Denmark
(author)
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Cao, YihaiKarolinska Institutet,Linköpings universitet,Avdelningen för kardiovaskulär medicin,Hälsouniversitetet,Department of Microbiology, Tumor, and Cell Biology, Karolinska Institute, Sweden(Swepub:liu)yihca64
(author)
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Karolinska InstitutetDepartment of Microbiology, Tumor, and Cell Biology, Karolinska Institute, Stockholm, Sweden
(creator_code:org_t)
Related titles
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In:Proceedings of the National Academy of Sciences of the United States of America: National Academy of Sciences109:39, s. 15894-158990027-84241091-6490
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Cao, Renhai
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Ji, Hong
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Feng, Ninghan
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Zhang, Yin
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Yang, Xiaojuan
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Andersson, Patri ...
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Sun, Yuping
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Tritsaris, Kater ...
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Dissing, Steen
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Cao, Yihai
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Linköping University
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Karolinska Institutet