The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index.
Blockade of vascular endothelial growth factor receptor-3 signaling inhibits fibroblast growth factor-2-induced lymphangiogenesis in mouse cornea
Open accessAbstract
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.
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Cites
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Induction of tumor lymphangiogenesis by VEGF-C promotes breast cancer metastasis
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Self-citationLYVE-1, a New Homologue of the CD44 Glycoprotein, Is a Lymph-specific Receptor for Hyaluronan
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Self-citationHyperplasia of Lymphatic Vessels in VEGF-C Transgenic Mice
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Self-citationVEGF-D promotes the metastatic spread of tumor cells via the lymphatics
Stacker, S. A., Caesar, C., Baldwin, M. E., Thornton, G. E., Williams, R. A., Prevo, R., Jackson, D. G., Nishikawa, S.-I., Kubo, H., & Achen, M. G. (2001) · Nature Medicine · doi:10.1038/84635 · Cited by 1,246
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Cited by
Mechanisms and regulation of endothelial VEGF receptor signalling
Simons, M., Gordon, E., & Claesson-Welsh, L. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.87 · Cited by 1,498
PDGF-BB induces intratumoral lymphangiogenesis and promotes lymphatic metastasis
Cao, R., Björndahl, M. A., Religa, P., Clasper, S., Garvin, S., Galter, D., Meister, B., Ikomi, F., Tritsaris, K., Dissing, S., et al. (2004) · Cancer Cell · doi:10.1016/j.ccr.2004.08.034 · Cited by 527
Self-citationLee, C., Kim, M.-J., Kumar, A., Lee, H.-W., Yang, Y., & Kim, Y. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02249-0 · Cited by 365
Cursiefen, C., Cao, J., Chen, L., Liu, Y., Maruyama, K., Jackson, D., Kruse, F. E., Wiegand, S. J., Dana, M. R., & Streilein, J. W. (2004) · Investigative Opthalmology & Visual Science · doi:10.1167/iovs.03-1380 · Cited by 329
The Lymphatic System in Health and Disease
Cueni, L. N., & Detmar, M. (2008) · Lymphatic Research and Biology · doi:10.1089/lrb.2008.1008 · Cited by 288
Metadata
- Authors
- Kubo, H., Cao, R., Bräkenhielm, E., Mäkinen, T., Cao, Y., & Alitalo, K.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2002-06-17
- Volume
- 99
- Issue
- 13
- Pages
- 8868-8873
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2078653335
- Cited by
- 305
- References
- 42
- FWCI
- 7.95
- Type
- journal article
- Language
- en
- Open access
- green
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- Kubo, H., Cao, R., Bräkenhielm, E., Mäkinen, T., Cao, Y., & Alitalo, K. (2002). Blockade of vascular endothelial growth factor receptor-3 signaling inhibits fibroblast growth factor-2-induced lymphangiogenesis in mouse cornea. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.062040199
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
