scholarly journals Early Growth Response-1 Induces and Enhances Vascular Endothelial Growth Factor-A Expression in Lung Cancer Cells

2010 ◽  
Vol 177 (1) ◽  
pp. 70-83 ◽  
Author(s):  
Hiroaki Shimoyamada ◽  
Takuya Yazawa ◽  
Hanako Sato ◽  
Koji Okudela ◽  
Jun Ishii ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Cancer Cells ◽  
Growth Response ◽  
Early Growth ◽  
Vascular Endothelial ◽  
Early Growth Response ◽  
Early Growth Response 1 ◽  
Endothelial Growth Factor

scholarly journals Antiangiogenic antitumor activities of IGFBP-3 are mediated by IGF-independent suppression of Erk1/2 activation and Egr-1–mediated transcriptional events

Blood ◽  
2011 ◽  
Vol 118 (9) ◽  
pp. 2622-2631 ◽  
Author(s):  
Jai-Hyun Kim ◽  
Dong Soon Choi ◽  
Ok-Hee Lee ◽  
Seung-Hyun Oh ◽  
Scott M. Lippman ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Cancer Cells ◽  
Small Cell ◽  
Vascular Endothelial ◽  
Small Cell Lung ◽  
Antitumor Activities ◽  
Endothelial Growth Factor ◽  
Igfbp 3

Abstract Most antiangiogenic therapies currently being evaluated in clinical trials target the vascular endothelial growth factor pathway; however, the tumor vasculature can acquire resistance to vascular endothelial growth factor-targeted therapy by shifting to other angiogenesis mechanisms. Insulin-like growth factor binding protein-3 (IGFBP-3) has been reported to suppress tumor growth and angiogenesis by both IGF-dependent and IGF-independent mechanisms; however, understanding of its IGF-independent mechanisms is limited. We observed that IGFBP-3 blocked tumor angiogenesis and growth in non–small cell lung cancer and head and neck squamous cell carcinoma. Conditioned media from an IGFBP-3–treated non–small cell lung cancer cell line displayed a significantly decreased capacity to induce HUVEC proliferation and aortic sprouting. In cancer cells, IGFBP-3 directly interacted with Erk1/2, leading to inactivation of Erk1/2 and Elk-1, and suppressed transcription of early growth response protein 1 and its target genes, basic fibroblast growth factor and platelet-derived growth factor. These data suggest that IGF-independent Erk1/2 inactivation and decreased IGFBP-3–induced Egr-1 expression block the autocrine and paracrine loops of angiogenic factors in vascular endothelial and cancer cells. Together, these findings provide a molecular framework of IGFBP-3's IGF-independent antiangiogenic antitumor activities. Future studies are needed for development of IGFBP-3 as a new line of antiangiogengic cancer drug.

scholarly journals Adenovirus-Mediated Transfer of BAX Driven by the Vascular Endothelial Growth Factor Promoter Induces Apoptosis in Lung Cancer Cells

2002 ◽  
Vol 6 (2) ◽  
pp. 190-198 ◽  
Author(s):  
Sergey A Kaliberov ◽  
Donald J Buchsbaum ◽  
G.Yancey Gillespie ◽  
David T Curiel ◽  
Waleed O Arafat ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Cancer Cells ◽  
Lung Cancer Cells ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor

scholarly journals Vascular endothelial growth factor activation of endothelial cells is mediated by early growth response-3

Blood ◽  
2010 ◽  
Vol 115 (12) ◽  
pp. 2520-2532 ◽  
Author(s):  
Jun-ichi Suehiro ◽  
Takao Hamakubo ◽  
Tatsuhiko Kodama ◽  
William C. Aird ◽  
Takashi Minami
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
Growth Response ◽  
Cell Activation ◽  
Early Growth ◽  
Vascular Endothelial ◽  
Endothelial Cell Activation ◽  
Early Growth Response ◽  
Endothelial Growth Factor

Endothelial cell activation and dysfunction underlie many vascular disorders, including atherosclerosis, tumor growth, and sepsis. Endothelial cell activation, in turn, is mediated primarily at the level of gene transcription. Here, we show that in response to several activation agonists, including vascular endothelial growth factor (VEGF), tumor necrosis factor-α, and thrombin, endothelial cells demonstrate rapid and profound induction of the early growth response (Egr) genes egr-1 and egr-3. In VEGF-treated endothelial cells, induction of Egr-3 was far greater and more prolonged compared with Egr-1. VEGF-mediated stimulation of Egr-3 involved the inducible binding of NFATc, serum response factor, and CREB to their respective consensus motifs in the upstream promoter region of Egr-3. Knockdown of Egr-3 markedly impaired VEGF-mediated proliferation, migration, and tube formation of endothelial cells and blocked VEGF-induced monocyte adhesion. Egr-3 knockdown abrogated VEGF-mediated vascular outgrowth from ex vivo aortic rings and attenuated Matrigel plug vascularization and melanoma tumor growth in vivo. Together, these findings suggest that Egr-3 is a critical determinant of VEGF signaling in activated endothelial cells. Thus, Egr-3 represents a potential therapeutic target in VEGF-mediated vasculopathic diseases.

scholarly journals Establishment of a Pre-vascularized 3D Lung Cancer Model in Fibrin Gel—Influence of Hypoxia and Cancer-Specific Therapeutics

2021 ◽  
Vol 9 ◽  
Author(s):  
Caroline Kniebs ◽  
Anja Elisabeth Luengen ◽  
Daniel Guenther ◽  
Christian Gabriel Cornelissen ◽  
Thomas Schmitz-Rode ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Cancer Cells ◽  
Model Systems ◽  
Vascular Endothelial ◽  
Cancer Model ◽  
Fibrin Gel ◽  
Lung Cancer Model ◽  
Endothelial Growth Factor

Lung cancer is the most frequently diagnosed cancer worldwide and the one that causes the highest mortality. In order to understand the disease and to develop new treatments, in vitro human lung cancer model systems which imitate the physiological conditions is of high significance. In this study, a human 3D lung cancer model was established that features the organization of a tumor with focus on tumor angiogenesis. Vascular networks were formed by co-culture of human umbilical vein endothelial cells and adipose tissue-derived mesenchymal stem cells (ASC) for 14 days in fibrin. A part of the pre-vascularized fibrin gel was replaced by fibrin gel containing lung cancer cells (A549) to form tri-cultures. This 3D cancer model system was cultured under different culture conditions and its behaviour after treatment with different concentrations of tumor-specific therapeutics was evaluated. The evaluation was performed by measurement of metabolic activity, viability, quantification of two-photon laser scanning microscopy and measurement of the proangiogenic factor vascular endothelial growth factor in the supernatant. Hypoxic conditions promoted vascularization compared to normoxic cultured controls in co- and tri-cultures as shown by significantly increased vascular structures, longer structures with a higher area and volume, and secretion of vascular endothelial growth factor. Cancer cells also promoted vascularization. Treatment with 50 µM gefitinib or 50 nM paclitaxel decreased the vascularization significantly. VEGF secretion was only reduced after treatment with gefitinib, while in contrast secretion remained constant during medication with paclitaxel. The findings suggest that the herein described 3D lung cancer model provides a novel platform to investigate the angiogenic potential of cancer cells and its responses to therapeutics. Thus, it can serve as a promising approach for the development and patient-specific pre-selection of anticancer treatment.

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