Cited by 694Angiogenesis and VEGF in CancerTGF-β signaling in diseasesLymphatic System and Diseases

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Vascular endothelial growth factor is induced in response to transforming growth factor-beta in fibroblastic and epithelial cells.

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Pertovaara, L., Kaipainen, A., Mustonen, T., Orpana, A., Ferrara, N., Saksela, O., Alitalo, K.·1994·Journal of Biological Chemistry

DOI 10.1016/s0021-9258(17)37365-9

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Abstract

Transforming growth factor beta (TGF-beta) is a multifunctional polypeptide that regulates the proliferation and differentiation of various cells and has an angiogenic effect in vivo, although it inhibits the growth of cultured endothelial cells. We report here that TGF-beta treatment of quiescent cultures of mouse embryo-derived AKR-2B cells, which are growth-stimulated by TGF-beta, and human lung adenocarcinoma A549 cells, which are growth-inhibited by TGF-beta, results in the induction of vascular endothelial growth factor (VEGF) mRNA and protein. Maximal VEGF mRNA levels occurred 4-8 h after stimulation with a decline to background levels in 24 h. In contrast, the related placenta growth factor mRNA was not induced by TGF-beta in these cells. No VEGF receptor mRNA was seen in AKR-2B cells. Also, TGF-beta treatment of endothelial cells, which express the FLT1 and KDR/FLK-1 receptors for VEGF, did not cause VEGF induction. Because VEGF is known to be a strong angiogenic factor for endothelial cells, the results suggest that the angiogenic effect of TGF-beta on endothelial cells in blood vessels may be mediated at least partly by a paracrine induction of VEGF in other surrounding cell types.

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Authors: Pertovaara, L., Kaipainen, A., Mustonen, T., Orpana, A., Ferrara, N., Saksela, O., & Alitalo, K.
Affiliations: University of Helsinki (FI)
ORCID: Kaipainen, A.
Mustonen, T.
Ferrara, N.
Alitalo, K.
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 1994-03
Volume: 269
Issue: 9
Pages: 6271-6274
ISSN: 0021-9258 (ISSN-L)
DOI: 10.1016/s0021-9258(17)37365-9
OpenAlex: W1494416455
Cited by: 694
References: 38
Citations by year: 2025: 4 · 2024: 4 · 2023: 4 · 2022: 6 · 2021: 6 · 2020: 10 · 2019: 7 · 2018: 9 · 2017: 11 · 2016: 9 · 2015: 13 · 2014: 20 · 2013: 16 · 2012: 25
FWCI: 10.52
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 9745 d)
Locations: Journal of Biological Chemistry (publishedVersion, cc-by)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
Health Sciences › Medicine › Oncology › Lymphatic System and Diseases
Keywords: vascular endothelial growth factor, TGF-beta, angiogenesis, paracrine signaling, placental growth factor, VEGF receptors, Flt-1, KDR/Flk-1, A549 cells, lung adenocarcinoma, endothelial cells, fibroblasts, epithelial cells, VEGF mRNA expression
MeSH terms: Animals, Cattle, Cell Line, Cells, Cultured, Endothelium, Vascular, Epithelium, Fibroblasts, Humans, Hybrid Cells, Lung Neoplasms, Lymphokines, Mice, Inbred AKR, Recombinant Proteins, Tumor Cells, Cultured, Umbilical Veins, Immunoblotting, Transforming Growth Factor beta, Endothelial Growth Factors, Vascular Endothelial Growth Factors, Vascular Endothelial Growth Factor A, Mice

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Vascular endothelial growth factor is induced in response to transforming growth factor-beta in fibroblastic and epithelial cells.

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