Open AccessJournal Article
Vascular Endothelial Growth Factor Is an Autocrine Survival Factor for Neuropilin-expressing Breast Carcinoma Cells
Robin E. Bachelder,Aimee M. Crago,Jun Chung,Melissa A. Wendt,Leslie M. Shaw,Gregory Robinson,Arthur M. Mercurio +6 more
TLDR
A novel function for the vascular endothelial growth factor (VEGF) in its ability to stimulate an autocrine signaling pathway in metastatic breast carcinoma cells that is essential for their survival is identified.Abstract:
We identify a novel function for the vascular endothelial growth factor (VEGF) in its ability to stimulate an autocrine signaling pathway in metastatic breast carcinoma cells that is essential for their survival. Suppression of VEGF expression in metastatic cells in vitro induced their apoptosis, in addition to inhibiting the constitutively elevated phosphatidylinositol 3'-kinase activity that is characteristic of these cells and important for their survival. Hypoxia enhanced the survival of metastatic cells by increasing VEGF expression. The importance of the VEGF receptor neuropilin was indicated by the ability of a neuropilin-binding VEGF isoform to enhance breast carcinoma survival. Moreover, the expression of neuropilin in neuropilin-deficient breast carcinoma cells protected them from apoptosis. The identification of this VEGF autocrine signaling pathway has important implications for tumor metastasis and therapeutic intervention.read more
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VEGF-targeted therapy: mechanisms of anti-tumour activity
Lee M. Ellis,Daniel J. Hicklin +1 more
TL;DR: Several vascular endothelial growth factor (VEGF)-targeted agents, administered either as single agents or in combination with chemotherapy, have been shown to benefit patients with advanced-stage malignancies.
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Vascular Permeability Factor/Vascular Endothelial Growth Factor: A Critical Cytokine in Tumor Angiogenesis and a Potential Target for Diagnosis and Therapy
TL;DR: Recognized as the single most important angiogenic cytokine, VEGF-A has a central role in tumor biology and will likely have an important role in future approaches designed to evaluate patient prognosis and may also become an important target for cancer therapy.
Journal ArticleDOI
Combination therapy in combating cancer.
Reza Bayat Mokhtari,Reza Bayat Mokhtari,Tina S. Homayouni,Narges Baluch,Evgeniya Morgatskaya,Sushil Kumar,Bikul Das,Herman Yeger +7 more
TL;DR: An approach that combines repurposed pharmaceutical agents with other therapeutics has shown promising results in mitigating tumour burden, and this systematic review discusses important pathways commonly targeted in cancer therapy.
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Glomerular-specific alterations of VEGF-A expression lead to distinct congenital and acquired renal diseases
Vera Eremina,Manish M. Sood,Jody J. Haigh,Andras Nagy,Ginette Lajoie,Napoleone Ferrara,Hans-Peter Gerber,Yamato Kikkawa,Jeffrey H. Miner,Susan E. Quaggin +9 more
TL;DR: The data demonstrate that tight regulation of VEGF-A signaling is critical for establishment and maintenance of the glomerular filtration barrier and strongly supports a pivotal role for VEGf-A in renal disease.
Journal ArticleDOI
Lessons from phase III clinical trials on anti-VEGF therapy for cancer
TL;DR: Adding bevacizumab to chemotherapy failed to increase survival in patients with previously treated and refractory metastatic breast cancer, and addition of vatalanib, a kinase inhibitor developed as a VEGF receptor-selective agent, to chemotherapy did not show a similar benefit in metastatic colorectal cancer patients.
References
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Journal ArticleDOI
Patterns and Emerging Mechanisms of the Angiogenic Switch during Tumorigenesis
TL;DR: The work from the authors' laboratories reviewed herein was supported by grants from the National Cancer Institute.
Journal ArticleDOI
Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis.
TL;DR: It is shown that vascular endothelial growth factor (VEGF) probably functions as a hypoxia-inducible angiogenic factor and is specifically induced in a subset of glioblastoma cells distinguished by their immediate proximity to necrotic foci and the clustering of capillaries alongside VEGF-producing cells.
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Neuropilin-1 Is Expressed by Endothelial and Tumor Cells as an Isoform-Specific Receptor for Vascular Endothelial Growth Factor
TL;DR: It is proposed that neuropilin-1 is a novel V EGF receptor that modulates VEGF binding to KDR and subsequent bioactivity and therefore may regulate VEGf-induced angiogenesis.
Journal ArticleDOI
Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumours
Thomas G. Graeber,Cynthia Osmanian,Tyler Jacks,David E. Housman,Cameron J. Koch,Scott W. Lowe,Scott W. Lowe,Amato J. Giaccia +7 more
TL;DR: It is proposed that hypoxia provides a physiological selective pressure in tumours for the expansion of variants that have lost their apoptotic potential, and in particular for cells acquiring p53mutations.
Journal ArticleDOI
Vascular Endothelial Growth Factor Regulates Endothelial Cell Survival through the Phosphatidylinositol 3′-Kinase/Akt Signal Transduction Pathway REQUIREMENT FOR Flk-1/KDR ACTIVATION
Hans-Peter Gerber,Amy McMurtrey,Joe Kowalski,Minhong Yan,Bruce Keyt,Vishva M. Dixit,Napoleone Ferrara +6 more
TL;DR: The Flk-1/KDR receptor and the PI3-kinase/Akt signal transduction pathway are identified as crucial elements in the processes leading to endothelial cell survival induced by VEGF, and inhibition of apoptosis may represent a major aspect of the regulatory activity of V EGF on the vascular endothelium.
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