The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.
VEGF-A induces tumor and sentinel lymph node lymphangiogenesis and promotes lymphatic metastasis
Open accessAbstract
The mechanisms of tumor metastasis to the sentinel lymph nodes are poorly understood. Vascular endothelial growth factor (VEGF)-A plays a principle role in tumor progression and angiogenesis; however, its role in tumor-associated lymphangiogenesis and lymphatic metastasis has remained unclear. We created transgenic mice that overexpress VEGF-A and green fluorescent protein specifically in the skin, and subjected them to a standard chemically-induced skin carcinogenesis regimen. We found that VEGF-A not only strongly promotes multistep skin carcinogenesis, but also induces active proliferation of VEGF receptor-2–expressing tumor-associated lymphatic vessels as well as tumor metastasis to the sentinel and distant lymph nodes. The lymphangiogenic activity of VEGF-A–expressing tumor cells was maintained within metastasis-containing lymph nodes. The most surprising finding of our study was that even before metastasizing, VEGF-A–overexpressing primary tumors induced sentinel lymph node lymphangiogenesis. This suggests that primary tumors might begin preparing their future metastatic site by producing lymphangiogenic factors that mediate their efficient transport to sentinel lymph nodes. This newly identified mechanism of inducing lymph node lymphangiogenesis likely contributes to tumor metastasis, and therefore, represents a new therapeutic target for advanced cancer and/or for the prevention of metastasis.
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Citations
Cites
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Self-citationDiscovery and development of bevacizumab, an anti-VEGF antibody for treating cancer
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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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VEGF-D promotes the metastatic spread of tumor cells via the lymphatics
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Vascular endothelial growth factor-C-mediated lymphangiogenesis promotes tumour metastasis
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Cited by
Pre-metastatic niches: organ-specific homes for metastases
Peinado, H., Zhang, H., Matei, I. R., Costa-Silva, B., Hoshino, A., Rodrigues, G., Psaila, B., Kaplan, R. N., Bromberg, J. F., Kang, Y., et al. (2017) · Nature Reviews Cancer · doi:10.1038/nrc.2017.6 · Cited by 1,889
The metastatic niche: adapting the foreign soil
Psaila, B., & Lyden, D. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2621 · Cited by 1,300
Integrins in angiogenesis and lymphangiogenesis
Avraamides, C. J., Garmy-Susini, B., & Varner, J. A. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2353 · Cited by 1,050
The hypoxic tumour microenvironment
Petrova, V., Annicchiarico-Petruzzelli, M., Melino, G., & Amelio, I. (2018) · Oncogenesis · doi:10.1038/s41389-017-0011-9 · Cited by 1,019
Metastasis: recent discoveries and novel treatment strategies
Eccles, S. A., & Welch, D. R. (2007) · The Lancet · doi:10.1016/s0140-6736(07)60781-8 · Cited by 721
Metadata
- Authors
- Hirakawa, S., Kodama, S., Kunstfeld, R., Kajiya, K., Brown, L. F., & Detmar, M.
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2005-04-04
- Volume
- 201
- Issue
- 7
- Pages
- 1089-1099
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- OpenAlex
- W2031563062
- Cited by
- 719
- References
- 39
- FWCI
- 22.33
- Type
- journal article
- Language
- en
- Open access
- green
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- Hirakawa, S., Kodama, S., Kunstfeld, R., Kajiya, K., Brown, L. F., & Detmar, M. (2005). VEGF-A induces tumor and sentinel lymph node lymphangiogenesis and promotes lymphatic metastasis. The Journal of Experimental Medicine. https://doi.org/10.1084/jem.20041896
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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