Hypoxia inducible factor-1α correlates with VEGF-C expression and lymphangiogenesis in breast cancer
Abstract
The transcription factor Hypoxia inducible factor-1alpha (HIF-1alpha) plays a crucial role in tumor progression by regulating angiogenesis, cell survival and drug resistance. HIF-1alpha is also implicated in biological functions under normoxic conditions and recent data provide evidence for a possible role in tumor lymphangiogenesis by regulating the lymphatic vascular endothelial growth factor-C (VEGF-C). In breast cancer, lymphatic vessel invasion (LVI) by tumor cells and subsequent metastasis to axillary lymph nodes is a critical point in progression of the disease with severe therapeutical and prognostic implications. Aim of this study is to investigate the role of HIF-1alpha in VEGF-C expression, lymphangiogenesis, and LVI in lymph node positive breast cancer. Lymphatic microvessel density (LMVD), LVI, HIF-1alpha and VEGF-C protein-expression were evaluated by immunohistochemistry in 119 cases of lymph node positive invasive breast cancer. There was a significant correlation between HIF-1alpha and VEGF-C (p = 0.026, r = 0.204, Spearman's coefficient of correlation). Further a significant association between HIF-1alpha-expression and the amount of peritumoral lymphangiogenesis LMVD was seen (p = 0.014, Mann-Whitney test). LMVD correlated significantly with LVI (p<0.001, Mann-Whitney test). HIF-1alpha was an independent prognostic factor for overall and disease free survival in uni- and multivariate analysis (p = 0.027, 0.029, 0.025, respectively, Cox regression). Our data…
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Hypoxia-induced VEGF production promotes lymph- and angiogenesis, which facilitate tumor cell intravasation and dissemination.
“Hypoxia-induced VEGF production promotes lymph-and angiogenesis, which facilitate tumor cell intravasation and dissemination (Claffey et al., 1996;Schoppmann et al., 2006).”
From Therapeutic targeting of hypoxia and hypoxia-inducible factors in cancer (2016) · cites this paper as Schoppmann et al., 2006
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Hsp90 regulates a von Hippel Lindau-independent hypoxia-inducible factor-1α-degradative pathway
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Hypoxia in cancer: significance and impact on clinical outcome
Vaupel, P., & Mayer, A. (2007) · Cancer and Metastasis Reviews · doi:10.1007/s10555-007-9055-1 · Cited by 2,240 · see citing works
Therapeutic targeting of hypoxia and hypoxia-inducible factors in cancer
Wigerup, C., Påhlman, S., & Bexell, D. (2016) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2016.04.009 · Cited by 687 · see citing works
“Hypoxia-induced VEGF production promotes lymph- and angiogenesis,which facilitate tumor cell intravasation and dissemination (Claffey et al., 1996; Schoppmann et al., 2006).”
BackgroundRole of hypoxia-inducible factors in breast cancer metastasis
Gilkes, D. M., & Semenza, G. L. (2013) · Future Oncology · doi:10.2217/fon.13.92 · Cited by 274 · see citing works
Schito, L., Rey, S., Tafani, M., Zhang, H., Wong, C. C.-L., Russo, A., Russo, M. A., & Semenza, G. L. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1214019109 · Cited by 224 · see citing works
- Authors
- Schoppmann, S. F., Fenzl, A., Schindl, M., Bachleitner-Hofmann, T., Nagy, K., Gnant, M., Horvat, R., Jakesz, R., & Birner, P.
- Affiliations
- University of Vienna (AT)
- Corresponding author
- Schoppmann, Sebastian F.
- Venue
- Breast Cancer Research and Treatment
- Published
- 2006-03-23
- Volume
- 99
- Issue
- 2
- Pages
- 135-141
- ISSN
- 0167-6806 (ISSN-L)
- 1573-7217
- OpenAlex
- W2009598951
- Cited by
- 106
- References
- 1
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 1 · 2023: 3 · 2022: 8 · 2021: 4 · 2020: 4 · 2019: 3 · 2018: 4 · 2017: 5 · 2016: 2 · 2015: 3 · 2014: 5 · 2013: 13 · 2012: 13
- FWCI
- 3.13
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Breast Cancer Research and Treatment (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Lymphatic System and Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Keywords
- hypoxia-inducible factor-1α, VEGF-C, lymphangiogenesis, breast cancer, lymphatic vessel invasion, lymph node metastasis, lymphatic microvessel density, prognostic factors, tumor progression, therapeutic target
- MeSH terms
- Adult, Aged, Breast Neoplasms, Female, Humans, Lymphatic Metastasis, Middle Aged, Neoplasm Invasiveness, Neoplasm Staging, Carcinoma, Ductal, Breast, Carcinoma, Lobular, Disease-Free Survival, Vascular Endothelial Growth Factor C, Lymphangiogenesis, Lymphatic Vessels, Hypoxia-Inducible Factor 1, alpha Subunit
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