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Collaborative inter...
Collaborative interplay between FGF-2 and VEGF-C promotes lymphangiogenesis and metastasis
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- Cao, Renhai (author)
- Karolinska Institutet
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- Ji, Hong (author)
- Karolinska Institutet
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- Feng, Ninghan (author)
- Department of Microbiology, Tumor, and Cell Biology, Karolinska Institute, Stockholm, Sweden
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- Zhang, Yin (author)
- Karolinska Institutet
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- Yang, Xiaojuan (author)
- Department of Microbiology, Tumor, and Cell Biology, Karolinska Institute, Stockholm, Sweden
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- Andersson, Patrik (author)
- Karolinska Institutet
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- Sun, Yuping (author)
- Department of Oncology, Jinan Central Hospital, Shandong University, Jinan, Shandong , People's Republic of China
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- Tritsaris, Katerina (author)
- Department of Cellular and Molecular Medicine, Center for Healthy Aging Panum Institute, University of Copenhagen, Copenhagen, Denmark
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- Jon Hansen, Anker (author)
- Department of Neuroscience and Pharmacology, Panum Institute, University of Copenhagen, Copenhagen, Denmark and Novo Nordisk A/S Måløv, Denmark
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- Dissing, Steen (author)
- Department of Cellular and Molecular Medicine, Center for Healthy Aging Panum Institute, University of Copenhagen, Copenhagen, Denmark
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- Cao, Yihai (author)
- Karolinska Institutet,Linköpings universitet,Avdelningen för kardiovaskulär medicin,Hälsouniversitetet,Department of Microbiology, Tumor, and Cell Biology, Karolinska Institute, Sweden
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(creator_code:org_t)
- 2012-09-11
- 2012
- English.
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In: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 109:39, s. 15894-15899
- Related links:
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https://www.pnas.org...
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https://urn.kb.se/re...
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Abstract
Subject headings
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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.
Keyword
- neovascularization
- growth factors
- signaling interplay
- cancer spread
- antiangiogenic therapy
- SOCIAL SCIENCES
- SAMHÄLLSVETENSKAP
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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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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show more...
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Sun, Yuping
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Tritsaris, Kater ...
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Jon Hansen, Anke ...
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Dissing, Steen
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Cao, Yihai
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- Articles in the publication
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Proceedings of t ...
- By the university
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Linköping University
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Karolinska Institutet