scholarly journals Vascular Endothelial Growth Factor Receptor-1 Activation Mediates Epithelial to Mesenchymal Transition in Human Pancreatic Carcinoma Cells

2006 ◽  
Vol 66 (1) ◽  
pp. 46-51 ◽  
Author(s):  
Anthony D. Yang ◽  
E. Ramsay Camp ◽  
Fan Fan ◽  
Lanlan Shen ◽  
Michael J. Gray ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Pancreatic Carcinoma ◽  
Epithelial To Mesenchymal Transition ◽  
Growth Factor Receptor ◽  
Carcinoma Cells ◽  
Vascular Endothelial ◽  
Mesenchymal Transition ◽  
Endothelial Growth Factor

scholarly journals Population heterogeneity in the epithelial to mesenchymal transition is controlled by NFAT and phosphorylated Sp1

2015 ◽  
Author(s):  
Russell Gould ◽  
David Bassen ◽  
Anirikh Chakrabarti ◽  
Jeffrey Varner ◽  
Jonathan Butcher
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Epithelial To Mesenchymal Transition ◽  
Population Heterogeneity ◽  
Vascular Endothelial ◽  
Mesenchymal Transition ◽  
Hybrid State ◽  
Cellular Population ◽  
Signaling Axis ◽  
Endothelial Growth Factor

Epithelial to mesenchymal transition (EMT) is an essential differentiation program during tissue morphogenesis and remodeling. EMT is induced by soluble transforming growth factor β (TGF-β) family members, and restricted by vascular endothelial growth factor fam- ily members. While many downstream molecular regulators of EMT have been identified, these have been largely evaluated individually without considering potential crosstalk. In this study, we created an ensemble of dynamic mathematical models describing TGF-β induced EMT to better understand the operational hierarchy of this complex molecular pro- gram. We used ordinary differential equations (ODEs) to describe the transcriptional and post-translational regulatory events driving EMT. Model parameters were estimated from multiple data sets using multiobjective optimization, in combination with cross-validation. TGF-β exposure drove the model population toward a mesenchymal phenotype, while an epithelial phenotype was enhanced following vascular endothelial growth factor A (VEGF- A) exposure. Simulations predicted that the transcription factors phosphorylated SP1 and NFAT were master regulators promoting or inhibiting EMT, respectively. Surprisingly, simulations also predicted that a cellular population could exhibit phenotypic heterogene- ity (characterized by a significant fraction of the population with both high epithelial and mesenchymal marker expression) if treated simultaneously with TGF-β and VEGF-A. We tested this prediction experimentally in both MCF10A and DLD1 cells and found that up- wards of 45% of the cellular population acquired this hybrid state in the presence of both TGF-β and VEGF-A. We experimentally validated the predicted NFAT/Sp1 signaling axis for each phenotype response. Lastly, we found that cells in the hybrid state had signifi- cantly different functional behavior when compared to VEGF-A or TGF-β treatment alone. Together, these results establish a predictive mechanistic model of EMT susceptibility, and potentially reveal a novel signaling axis which regulates carcinoma progression through an EMT versus tubulogenesis response.

The Association between the Vascular Endothelial Growth Factor–to–Cancer Antigen 125 Ratio in Peritoneal Dialysis Effluent and the Epithelial-to-Mesenchymal Transition in Continuous Ambulatory Peritoneal Dialysis

2008 ◽  
Vol 28 (3_suppl) ◽  
pp. 101-106 ◽  
Author(s):  
Jun-Young Do ◽  
Yong-Lim Kim ◽  
Jong-Won Park ◽  
Kyung-Ae Chang ◽  
Seung-Hyun Lee ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Peritoneal Dialysis ◽  
Growth Factors ◽  
Growth Factor ◽  
Epithelial To Mesenchymal Transition ◽  
Vascular Endothelial ◽  
Cancer Antigen 125 ◽  
Cancer Antigen ◽  
Mesenchymal Transition ◽  
Endothelial Growth Factor

We examined peritoneal growth factors, mesothelial mass, and epithelial-to-mesenchymal transition (EMT) in response to peritoneal exposure to peritoneal dialysate with standard and low concentrations of glucose degradation products (GDPs). We randomized 56 incident continuous ambulatory peritoneal dialysis (CAPD) patients to receive either low-GDP (30 patients) or high-GDP (standard) peritoneal dialysis (PD) solution (26 patients). The effects of the PD solutions on EMT and peritoneal growth factors in overnight dialysate effluent were compared at 1, 6, and 12 months. Assessment of EMT was performed after human peritoneal mesothelial cells (HPMCs) were cultured from overnight effluent. The low-GDP solution group showed significantly higher dialysate levels of cancer antigen 125 (CA125), fibronectin, transforming growth factor β(TGFβ)–induced gene product (βig-h3), and interleukin-6 (IL-6), but the rate of EMT was significantly lower in the low-GDP solution group during the initial 12 months of CAPD treatment. After adjusting peritoneal growth factors for dialysate CA125 concentration, the low-GDP solution group showed significantly lower ratios of fibronectin/CA125, βig-h3/CA125, IL-6/CA125, TGFβ/CA125, and vascular endothelial growth factor (VEGF)/CA125 than did patients in the high-GDP (standard) solution group. Factors associated with higher EMT were the type of solution (high in GDPs), the mass of HPMCs (low CA125), and higher VEGF/CA125. Adjustment of dialysate VEGF for effluent CA125 revealed a significant association with EMT. It suggests that fibroblastoid transition from HPMCs could be affected by the intraperitoneal VEGF per unit mass of HPMCs.

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