scholarly journals Endometrial Stromal Decidualization Responds Reversibly to Hormone Stimulation and Withdrawal

Endocrinology ◽  
2016 ◽  
Vol 157 (6) ◽  
pp. 2432-2446 ◽  
Author(s):  
Jie Yu ◽  
Sarah L. Berga ◽  
Erika B. Johnston-MacAnanny ◽  
Neil Sidell ◽  
Indrani C. Bagchi ◽  
...  

Human endometrial stromal decidualization is required for embryo receptivity, angiogenesis, and placentation. Previous studies from our laboratories established that connexin (Cx)-43 critically regulates endometrial stromal cell (ESC) differentiation, whereas gap junction blockade prevents it. The current study evaluated the plasticity of ESC morphology and Cx43 expression, as well as other biochemical markers of cell differentiation, in response to decidualizing hormones. Primary human ESC cultures were exposed to 10 nM estradiol, 100 nM progesterone, and 0.5 mM cAMP for up to 14 days, followed by hormone withdrawal for 14 days, mimicking a biphasic ovulatory cycle. Reversible differentiation was documented by characteristic changes in cell shape. Cx43 was reversibly up- and down-regulated after the estradiol, progesterone, and cAMP treatment and withdrawal, respectively, paralleled by fluctuations in prolactin, vascular endothelial growth factor, IL-11, and glycodelin secretion. Markers of mesenchymal-epithelial transition (MET), and its counterpart epithelial-mesenchymal transition, followed reciprocal patterns corresponding to the morphological changes. Incubation in the presence of 18α-glycyrrhetinic acid, an inhibitor of gap junctions, partially reversed the expression of decidualization and MET markers. In the absence of hormones, Cx43 overexpression promoted increases in vascular endothelial growth factor and IL-11 secretion, up-regulated MET markers, and reduced N-cadherin, an epithelial-mesenchymal transition marker. The combined results support the hypothesis that Cx43-containing gap junctions and endocrine factors cooperate to regulate selected biomarkers of stromal decidualization and MET and suggest roles for both phenomena in endometrial preparation for embryonic receptivity.

2019 ◽  
Vol 56 (6) ◽  
pp. 826-839 ◽  
Author(s):  
Krystal Harris ◽  
Howard B. Gelberg ◽  
Matti Kiupel ◽  
Stuart C. Helfand

Feline oral squamous cell carcinoma (FOSCC) is an aggressive malignancy with invasive and metastatic behavior. It is poorly responsive to chemotherapy and radiation. Neoplastic epithelial-mesenchymal transition (EMT) portends highly malignant behavior and enhances resistance to therapy. In transitioning to a more malignant phenotype, carcinoma stem cells undergo transformation mediated by expression of proteins, endowing them with mesenchymal properties advantageous to cell survival. The goal of the current study was to identify proteins associated with EMT in FOSCC. This study documents protein expression patterns in 10 FOSCC biopsies and 3 FOSCC cell lines (SCCF1, SCCF2, SCCF3), compatible with an EMT phenotype. As markers of EMT, P-cadherin, N-cadherin, vimentin, nuclear transcription factors Twist and Snail, hypoxia inducible factor 1α (HIF-1α), programmed death ligand 1, and vascular endothelial growth factor D, as well as E-cadherin, were examined using immunohistochemistry, Western blot, and enzyme-linked immunosorbent assay. P-cadherin, Twist, HIF-1α, and programmed death ligand 1 were commonly expressed in biopsies and cell lines. N-cadherin, classically associated with EMT, was not highly expressed, and E-cadherin was coexpressed along with proteins characteristic of EMT in all specimens. Production of vascular endothelial growth factor A by cell lines, a process regulated by HIF-1α expression, was suppressed by the small-molecule inhibitor dasatinib. These data are consistent with EMT in FOSCC and shed light on cellular changes that could contribute to the aggressive behavior of FOSCC.


Cancers ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 48 ◽  
Author(s):  
Chon Phin Ong ◽  
Wai Leong Lee ◽  
Yin Quan Tang ◽  
Wei Hsum Yap

Cancer is characterised by uncontrolled cell division and abnormal cell growth, which is largely caused by a variety of gene mutations. There are continuous efforts being made to develop effective cancer treatments as resistance to current anticancer drugs has been on the rise. Natural products represent a promising source in the search for anticancer treatments as they possess unique chemical structures and combinations of compounds that may be effective against cancer with a minimal toxicity profile or few side effects compared to standard anticancer therapy. Extensive research on natural products has shown that bioactive natural compounds target multiple cellular processes and pathways involved in cancer progression. In this review, we discuss honokiol, a plant bioactive compound that originates mainly from the Magnolia species. Various studies have proven that honokiol exerts broad-range anticancer activity in vitro and in vivo by regulating numerous signalling pathways. These include induction of G0/G1 and G2/M cell cycle arrest (via the regulation of cyclin-dependent kinase (CDK) and cyclin proteins), epithelial–mesenchymal transition inhibition via the downregulation of mesenchymal markers and upregulation of epithelial markers. Additionally, honokiol possesses the capability to supress cell migration and invasion via the downregulation of several matrix-metalloproteinases (activation of 5′ AMP-activated protein kinase (AMPK) and KISS1/KISS1R signalling), inhibiting cell migration, invasion, and metastasis, as well as inducing anti-angiogenesis activity (via the down-regulation of vascular endothelial growth factor (VEGFR) and vascular endothelial growth factor (VEGF)). Combining these studies provides significant insights for the potential of honokiol to be a promising candidate natural compound for chemoprevention and treatment.


2017 ◽  
Vol 104 (3) ◽  
pp. 932-939 ◽  
Author(s):  
Ben M.-W. Illigens ◽  
Alejandra Casar Berazaluce ◽  
Dimitrios Poutias ◽  
Robert Gasser ◽  
Pedro J. del Nido ◽  
...  

2019 ◽  
Vol 104 (8) ◽  
pp. 1085-1088 ◽  
Author(s):  
Avi Ohayon ◽  
Irene De Rosa ◽  
Oudy Semoun ◽  
Camille Jung ◽  
Donato Colantuono ◽  
...  

AimsTo demonstrate and evaluate the morphological changes of multilayered fibrovascular pigment epithelial detachment (PED) to a single anti-vascular endothelial growth factor (VEGF) injection in age-related macular degeneration (AMD).MethodsWe retrospectively analysed the morphological changes of 30 eyes with exudative AMD showing fibrotic multilayered PED, between two consecutive visits. All patients had one anti-VEGF intravitreal injection at the first visit. We quantitatively analysed the different compartments within the PED and their morphological response.ResultsThe mean follow-up time interval between the first and the second visit was 32.46±4.64 days. We defined three optical coherence tomography zones within the PED: a subretinal pigment epithelium inhomogeneous hyporeflective space (layer 1), a hyper-reflective band beneath layer 1 (layer 2), and a hyporeflective space between the Bruch’s membrane and layer 2 (layer 3). The mean height of layer 1 was 142±44.63 and 99.30±39.79 µm at visits 1 and 2, respectively. The mean thickness of layer 2 was 101.42±46.66 and 82.76±35.24 µm at visits 1 and 2, respectively. The mean height of layer 3 was 35.77±32.77 and 5.66±8.68 µm at visits 1 and 2, respectively (p=0.009). The mean height change for layer 1 was statistically significantly higher than for layer 2 (p=0.0002).ConclusionsFibrovascular PED was compartmented into three layers with different reflectivities that morphologically responded differently to a single anti-VEGF injection. Layer 2 had a statistically significantly lower response compared with layer 1, suggesting the hypothesis of a fibrotic component in layer 2.


2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
Sonoo Mizuiri ◽  
Hiromichi Hemmi ◽  
Michitsune Arita ◽  
Reibin Tai ◽  
Yoshinari Hattori ◽  
...  

Objectives. Epithelial mesenchymal transition (EMT) is important for peritoneal deterioration. We evaluated the association between peritoneal solute transport rate (PSTR) and effluent markers related to EMT with adjusted values for effluent cancer antigen 125 (CA125).Methods. One hundred five incident peritoneal dialysis (PD) patients on PD for 25 (12–68) months with biocompatible solutions were included in the study. Fast peritoneal equilibration test was used to evaluate PSTR. Effluent hepatocyte growth factor (HGF), bone morphogenic protein-7 (BMP-7), vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), and CA125 at 4 h were measured.Results. Patients with dialysate/plasma creatinine ≧0.82 showed significantly higher effluent HGF (240 versus 133 pg/mL, ), VEGF, IL-6, and IL6/CA125 levels than the others but no significant differences in effluent HGF/CA125, BMP-7, and BMP7/CA125 were observed.Conclusion. Increase in the effluent HGF levels as a compensatory mechanism is a marker of peritoneal deterioration, but controversy remains regarding adjusted value for CA125.


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