Blockade of vascular endothelial growth factor receptor-3 signaling inhibits fibroblast growth factor-2-induced lymphangiogenesis in mouse cornea.

Kubo, Hajime (författare)

Brakenhielm, Ebba (författare)

Mäkinen, Taija (författare)

Alitalo, Kari (författare)

(creator_code:org_t)

2002-06-17
2002
Engelska.
Ingår i: 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

Relaterad länk:: http://www.pnas.org/...; visa fler...; https://urn.kb.se/re...; https://doi.org/10.1...; http://kipublication...; visa färre...

Abstract Ämnesord

Stäng

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.

Av författaren/redakt...: Kubo, Hajime; Cao, Renhai; Brakenhielm, Ebb ...; Mäkinen, Taija; Cao, Yihai; Alitalo, Kari

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