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Blockade of vascula...
Blockade of vascular endothelial growth factor receptor-3 signaling inhibits fibroblast growth factor-2-induced lymphangiogenesis in mouse cornea.
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Kubo, Hajime (author)
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- Cao, Renhai (author)
- Karolinska Institutet
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Brakenhielm, Ebba (author)
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Mäkinen, Taija (author)
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- Cao, Yihai (author)
- Karolinska Institutet
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Alitalo, Kari (author)
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(creator_code:org_t)
- 2002-06-17
- 2002
- English.
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 99:13
- Related links:
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http://www.pnas.org/...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Subject headings
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- Vascular endothelial growth factor receptor-3 (VEGFR-3) is a major mediator of lymphangiogenesis. Recently, VEGFR-3 ligands, VEGF-C, and VEGF-D were reported to promote tumor lymphangiogenesis and lymphatic metastasis, and these processes were inhibited by blocking of the VEGFR-3-signaling pathway. Here, we have adapted the mouse corneal angiogenesis assay to study potential lymphangiogenic factors and inhibitors. Immunohistochemical analysis with lymphatic endothelial markers showed that VEGF-C induces lymphatic as well as blood vessel growth in the cornea. By contrast, VEGF induced angiogenesis but not lymphangiogenesis. Fibroblast growth factor-2 (FGF-2) stimulated both lymphangiogenesis and angiogenesis. FGF-2 up-regulated VEGF-C expression in vascular endothelial and perivascular cells. Furthermore, administration of blocking anti-VEGFR-3 antibodies inhibited the FGF-2-induced lymphangiogenesis. These findings show that VEGFR-3 can mediate lymphangiogenesis induced by other growth factors. Because increased expression of FGF-2 and VEGF-C has been associated with lymphatic metastasis, our results provide a potential strategy for the inhibition of lymphatic metastasis in cancer therapy.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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