scholarly journals Form follows function: Morphological and immunohistological insights into epithelial–mesenchymal transition characteristics of tumor buds

Tumor Biology ◽  
2017 ◽  
Vol 39 (5) ◽  
pp. 101042831770550 ◽  
Author(s):  
Kathrin Enderle-Ammour ◽  
Moritz Bader ◽  
Theresa Dorothee Ahrens ◽  
Kai Franke ◽  
Sylvia Timme ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Zinc Finger ◽  
Cell Morphology ◽  
Epithelial Mesenchymal Transition ◽  
Three Dimensional ◽  
Tumor Budding ◽  
Mesenchymal Transition ◽  
Tumor Mass ◽  
E Box ◽  
E Cadherin

In cancer biology, the architectural concept “form follows function” is reflected by cell morphology, migration, and epithelial–mesenchymal transition protein pattern. In vivo, features of epithelial–mesenchymal transition have been associated with tumor budding, which correlates significantly with patient outcome. Hereby, the majority of tumor buds are not truly detached but still connected to a major tumor mass. For detailed insights into the different tumor bud types and the process of tumor budding, we quantified tumor cells according to histomorphological and immunohistological epithelial–mesenchymal transition characteristics. Three-dimensional reconstruction from adenocarcinomas (pancreatic, colorectal, lung, and ductal breast cancers) was performed as published. Tumor cell morphology and epithelial–mesenchymal transition characteristics (represented by zinc finger E-box-binding homeobox 1 and E-Cadherin) were analyzed qualitatively and quantitatively in a three-dimensional context. Tumor buds were classified into main tumor mass, connected tumor bud, and isolated tumor bud. Cell morphology and epithelial–mesenchymal transition marker expression were assessed for each tumor cell. Epithelial–mesenchymal transition characteristics between isolated tumor bud and connected tumor bud demonstrated no significant differences or trends. Tumor cell count correlated significantly with epithelial–mesenchymal transition and histomorphological characteristics. Regression curve analysis revealed initially a loss of membranous E-Cadherin, followed by expression of cytoplasmic E-Cadherin and subsequent expression of nuclear zinc finger E-box-binding homeobox 1. Morphologic changes followed later in this sequence. Our data demonstrate that connected and isolated tumor buds are equal concerning immunohistochemical epithelial–mesenchymal transition characteristics and histomorphology. Our data also give an insight in the process of tumor budding. While there is a notion that the epithelial–mesenchymal transition zinc finger E-box-binding homeobox 1–E-Cadherin cascade is initiated by zinc finger E-box-binding homeobox 1, our results are contrary and outline other possible pathways influencing the regulation of E-Cadherin.

scholarly journals Plasmacytoid urothelial carcinoma of renal pelvis with positive zinc finger E–box–binding homeobox 1: a case report

2020 ◽  
Author(s):  
Atsuko Takada-Owada ◽  
Yumi Nozawa ◽  
Masato Onozaki ◽  
Shuhei Noda ◽  
Tsengelumaa Jamiyan ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Zinc Finger ◽  
Renal Pelvis ◽  
Plasma Cells ◽  
Epithelial Mesenchymal Transition ◽  
Resected Specimen ◽  
Mesenchymal Transition ◽  
E Box ◽  
Tumor Transformation ◽  
E Cadherin

Abstract BackgroundThe tumor transformation mechanism of a plasmacytoid urothelial carcinoma remains unexplained. We describe the case of a plasmacytoid urothelial carcinoma of the renal pelvis in which the expression of zinc finger E–box–binding homeobox 1 (ZEB1), a key nuclear transcription factor in an epithelial–mesenchymal transition, is involved in tumor transformation.Case presentationThe patient had a left nephrectomy with the clinical diagnosis of left pelvic renal cancer. The resected specimen showed that the tumor surface comprised a noninvasive papillary urothelial carcinoma with the carcinoma in situ, and the invasive area comprised a plasmacytoid urothelial carcinoma characterized by the presence of single dyscohesive malignant cells that resembled plasma cells in a loose myxoid stroma. The noninvasive urothelial carcinoma was positive for cytokeratin and E–cadherin, and negative for vimentin and ZEB1. In contrast, the invasive plasmacytoid urothelial carcinoma was positive for cytokeratin and also vimentin and ZEB1, and negative for E–cadherin. Additionally, this component was immunoreactive for CD138 and CD38 that are immunohistochemical markers for plasma cells.ConclusionWe suggest that ZEB1 is involved in the plasmacytoid transformation by repressing the E–cadherin in a plasmacytoid urothelial carcinoma.

scholarly journals Plasmacytoid urothelial carcinoma of renal pelvis with positive zinc finger E–box–binding homeobox 1: a case report

2020 ◽  
Author(s):  
Atsuko Takada-Owada ◽  
Yumi Nozawa ◽  
Masato Onozaki ◽  
Shuhei Noda ◽  
Tsengelumaa Jamiyan ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Zinc Finger ◽  
Renal Pelvis ◽  
Plasma Cells ◽  
Epithelial Mesenchymal Transition ◽  
Resected Specimen ◽  
Mesenchymal Transition ◽  
E Box ◽  
Tumor Transformation ◽  
E Cadherin

Abstract BackgroundThe tumor transformation mechanism of a plasmacytoid urothelial carcinoma remains unexplained. We describe the case of a plasmacytoid urothelial carcinoma of the renal pelvis in which the expression of zinc finger E–box–binding homeobox 1 (ZEB1), a key nuclear transcription factor in an epithelial–mesenchymal transition, is involved in tumor transformation.Case presentationThe patient had a left nephrectomy with the clinical diagnosis of left pelvic renal cancer. The resected specimen showed that the tumor surface comprised a noninvasive papillary urothelial carcinoma with the carcinoma in situ, and the invasive area comprised a plasmacytoid urothelial carcinoma characterized by the presence of single dyscohesive malignant cells that resembled plasma cells in a loose myxoid stroma. The noninvasive urothelial carcinoma was positive for cytokeratin and E–cadherin, and negative for vimentin and ZEB1. In contrast, the invasive plasmacytoid urothelial carcinoma was positive for cytokeratin and also vimentin and ZEB1, and negative for E–cadherin. Additionally, this component was immunoreactive for CD138 and CD38 that are immunohistochemical markers for plasma cells.ConclusionWe suggest that ZEB1 is involved in the plasmacytoid transformation by repressing the E–cadherin in a plasmacytoid urothelial carcinoma.

scholarly journals The functional activity of E-cadherin controls tumor cell metastasis at multiple steps

2020 ◽  
Vol 117 (11) ◽  
pp. 5931-5937 ◽  
Author(s):  
Tae-Young Na ◽  
Leslayann Schecterson ◽  
Alisha M. Mendonsa ◽  
Barry M. Gumbiner
Keyword(s):  
Tumor Cell ◽  
Tumor Cells ◽  
Functional Activity ◽  
Epithelial Mesenchymal Transition ◽  
Important Determinant ◽  
Three Dimensional ◽  
Metastatic Potential ◽  
Primary Tumors ◽  
Mesenchymal Transition ◽  
E Cadherin

E-cadherin is a tumor suppressor protein, and the loss of its expression in association with the epithelial mesenchymal transition (EMT) occurs frequently during tumor metastasis. However, many metastases continue to express E-cadherin, and a full EMT is not always necessary for metastasis; also, positive roles for E-cadherin expression in metastasis have been reported. We hypothesize instead that changes in the functional activity of E-cadherin expressed on tumor cells in response to environmental factors is an important determinant of the ability of the tumor cells to metastasize. We find that E-cadherin expression persists in metastatic lung nodules and circulating tumor cells (CTCs) in two mouse models of mammary cancer: genetically modified MMTV-PyMT mice and orthotopically grafted 4T1 tumor cells. Importantly, monoclonal antibodies that bind to and activate E-cadherin at the cell surface reduce lung metastasis from endogenous genetically driven tumors and from tumor cell grafts. E-cadherin activation inhibits metastasis at multiple stages, including the accumulation of CTCs from the primary tumor and the extravasation of tumor cells from the vasculature. These activating mAbs increase cell adhesion and reduce cell invasion and migration in both cell culture and three-dimensional spheroids grown from primary tumors. Moreover, activating mAbs increased the frequency of apoptotic cells without affecting proliferation. Although the growth of the primary tumors was unaffected by activating mAbs, CTCs and tumor cells in metastatic nodules exhibited increased apoptosis. Thus, the functional state of E-cadherin is an important determinant of metastatic potential beyond whether the gene is expressed.

scholarly journals Plasmacytoid urothelial carcinoma of renal pelvis with positive zinc finger E–box–binding homeobox 1: a case report

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Atsuko Takada-Owada ◽  
Yumi Nozawa ◽  
Masato Onozaki ◽  
Shuhei Noda ◽  
Tsengelmaa Jamiyan ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Zinc Finger ◽  
Renal Pelvis ◽  
Plasma Cells ◽  
Epithelial Mesenchymal Transition ◽  
Resected Specimen ◽  
Mesenchymal Transition ◽  
E Box ◽  
Tumor Transformation ◽  
E Cadherin

Abstract Background The tumor transformation mechanism of a plasmacytoid urothelial carcinoma remains unexplained. We describe the case of a plasmacytoid urothelial carcinoma of the renal pelvis in which the expression of zinc finger E–box–binding homeobox 1 (ZEB1), a key nuclear transcription factor in an epithelial–mesenchymal transition, is involved in tumor transformation. Case presentation The patient had a left nephrectomy with the clinical diagnosis of left pelvic renal cancer. The resected specimen showed that the tumor surface comprised a noninvasive papillary urothelial carcinoma with the carcinoma in situ, and the invasive area comprised a plasmacytoid urothelial carcinoma characterized by the presence of single dyscohesive malignant cells that resembled plasma cells in a loose myxoid stroma. The noninvasive urothelial carcinoma was positive for cytokeratin and E–cadherin, and negative for vimentin and ZEB1. In contrast, the invasive plasmacytoid urothelial carcinoma was positive for cytokeratin and also vimentin and ZEB1, and negative for E–cadherin. Additionally, this component was immunoreactive for CD138 and CD38 that are immunohistochemical markers for plasma cells. Conclusion We suggest that ZEB1 is involved in the plasmacytoid transformation by repressing the E–cadherin in a plasmacytoid urothelial carcinoma.

Zinc finger E-box-binding homeobox 1 (ZEB1): A novel predictor for the prognosis in gastrointestinal tumors.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e23515-e23515
Author(s):  
Shenglan Yang ◽  
Jiang Min
Keyword(s):  
Zinc Finger ◽  
Epithelial Mesenchymal Transition ◽  
High Expression ◽  
Mesenchymal Transition ◽  
Cancer Breast ◽  
Female Rate ◽  
Significant Difference ◽  
E Box ◽  
Progression Of Disease ◽  
Low Expression

e23515 Background: The gastrointestinal stromal tumors (GISTs) are the most common soft tissue sarcoma arising anywhere along gastrointestinal tract. The advanced and metastatic GISTs are the leading cause in GISTs inducing death. GISTs are the most commonly resulted from KIT or PDGFRA activation mutation. Currently adjuvant therapy with imatinib also targets the KIT and PDGFRA signals, which significantly increases the relapse-free survival and overall survival. However, KIT and PDGFRA mutation are not completely responsible for the progression of disease, especially metastasis of GISTs. So, there could be other molecular mechanism in GISTs progression. ZEB1 (zinc finger E-box-binding homeobox 1), as a member in zinc finger and homeodomain transcriptional factor family, plays a key role in metastasis of some epithelial carcinomas, such as colorectal cancer, breast cancer and NSCLC. We present that ZEB1, as a vital molecular in epithelial-mesenchymal transition, could be a promising marker in predicting the prognosis in GISTs. Methods: Immunohistochemistry staining for paraffin-embedding slices from 157 patients firstly diagnosed as GIST is applied for detecting the ZEB1 expression. Clinical, pathological, molecular and survival time were analyzed. All performances were approved by the Medical Ethics Committee in the First Affiliated Hospital of Chongqing Medical University. Results: In 157 patients, metastasis was found in 87 patients. In 87 patients with metastasis, high expression of ZEB1 almost exhibited (80 high/96 VS 7 non or low/96), while non or low expression was frequently detected in patients without metastasis (50 non or low/70 VS 20 high/70) (p < 0.0001). There was no significant difference between high and non/low expression patients in gender (48% VS 46% for male rate; 52% VS 54% for female rate), age (53 vs 54 years for median age), primary location (esophagus 2% VS 1.8%; stomach 57% VS 52.6%; duodenum and small intestine 31% VS 31.6%; colorectum and anus 10% VS 14.0%), tumor size (0.5-24cm, median 9.7cm VS 1-25.5cm, median 10.1cm), mitotic index (55.0% VS 58.6% for > 5/50HPF; 45.0% VS 41.4% for ≤5/50HPF), and risk stratification (low/intermediate risk 60.7% VS 63%; high risk 39.3% VS 37%). In addition, the 5-year OS rate was considerably lower in patients with ZEB1 high expression than those with ZEB1 none or low expression at baseline (37% vs 86%; p = 0.011). Conclusions: High expression of ZEB1 facilitates metastasis and indicates the poor prognosis in GISTs. ZEB1 could be a novel predictor for GIST’s prognosis.

Three-Dimensional Invasion of Epithelial–Mesenchymal Transition–Positive Human Peritoneal Mesothelial Cells into Collagen Gel is Promoted by the Concentration Gradient of Fibronectin

2011 ◽  
Vol 31 (4) ◽  
pp. 477-485 ◽  
Author(s):  
Youhei Yamaguchi ◽  
Tatsuya Ishigaki ◽  
Koushi Sano ◽  
Kei-Ichi Miyamoto ◽  
Shinsuke Nomura ◽  
...  
Keyword(s):  
Concentration Gradient ◽  
Epithelial Mesenchymal Transition ◽  
Three Dimensional ◽  
Collagen Gel ◽  
Mesothelial Cells ◽  
Type I ◽  
Mesenchymal Transition ◽  
Peritoneal Mesothelial Cells ◽  
Human Peritoneal Mesothelial Cells ◽  
E Cadherin

BackgroundIn long-term peritoneal dialysis, myofibroblast-like cells found in the interstitium of the peritoneum are assumed to be a transformed type of mesothelial cell—epithelial-mesenchymal transition-positive [EMT(+)] human peritoneal mesothelial cells (HPMCs)—because they express a mesothelial marker, cytokeratin. However, no direct evidence about how these cells are able to invade from the mesothelium has yet been obtained.AimIn this study, we aimed to verify whether EMT(+) HPMCs would, in vitro, invade three-dimensionally along certain chemotactic factors.MethodsWe used reverse-transcriptase polymerase chain reaction to measure expression of Snail, E-cadherin, α5-integrin, and matrix metalloproteinase 2 (MMP2) messenger RNA (mRNA) in HPMCs exposed to 10 ng/mL transforming growth factor β1 (TGFβ1) and how that expression corresponds to cell motility, as represented by a video movie. We used the Transwell (12 μm pore diameter: Sigma-Aldrich, Tokyo, Japan) to construct a three-dimensional (3D) cell migration chamber. In the lower chamber, a concentration gradient of fibronectin (FN) or albumin(Alb) was formed in 0.1% type I collagen by diffusion ( C0= 22 nmol/L; concentration gradient: C / C0= 0.7). All cells beneath the membrane were counted 72 hours after 5x104EMT(+) HPMCs (HPMCs after a 48-hour exposure to 10 ng/mL TGFβ1) had been spread in the upper chamber.ResultsAfter 72 hours, the increased motility of HPMCs resulting from their exposure to 10 ng/mL TGFβ1 had returned to baseline, but they retained an elongated morphology. Expression of Snail and MMP2 mRNA reached maximum at 24 hours. Expression of E-cadherin declined, and expression of α5-integrin increased continuously. In the 3D invasion study, significantly enhanced invasion by EMT(+) but not EMT(-) HPMCs was clearly seen in the presence of a FN concentration gradient ( p < 0.01), although invasion by EMT(+) and EMT(-) HPMCs in the absence of a FN concentration gradient was not statistically significantly different. Compared with the EMT(+) control (no concentration gradient), invasion by EMT(+) HPMCs was 2.1 ± 0.5 times (p < 0.05) and 1.4 ± 0.4 times (p = nonsignificant) higher along the FN and Alb concentration gradients respectively. Increased invasion along the FN concentration gradient was significantly inhibited (p < 0.05) when the HPMCs were pre-incubated with 5 μg/mL RGDS (a blocker for α5-integrin to FN).ConclusionsWe conclude that EMT(+) HPMCs invade collagen gel along the FN concentration gradient because of specific binding to RGDS receptors, which bind integrins such as α5-integrin, upregulating invasion-related gene expression associated with synthesis of the cytoskeleton protein α smooth muscle actin.

Sa1787 Regulation of Chemotherapy Resistance Through Epithelial-Mesenchymal Transition by Zinc Finger E-Box-Binding Proteins

2012 ◽  
Vol 142 (5) ◽  
pp. S-326
Author(s):  
Shinya Ohashi ◽  
Seiji Naganuma ◽  
Mitsuteru Natsuizaka ◽  
Shingo Kagawa ◽  
Hideaki Kinugasa ◽  
...  
Keyword(s):  
Zinc Finger ◽  
Binding Proteins ◽  
Epithelial Mesenchymal Transition ◽  
Chemotherapy Resistance ◽  
Mesenchymal Transition ◽  
E Box

scholarly journals Regulation of E-cadherin

2005 ◽  
Vol 8 (3) ◽  
Author(s):  
Z. Yang ◽  
H. Zhang ◽  
R. Kumar
Keyword(s):  
Transcription Factors ◽  
Present Article ◽  
Zinc Finger ◽  
Molecular Basis ◽  
Epithelial Mesenchymal Transition ◽  
Major Contributor ◽  
Mesenchymal Transition ◽  
Snail Family ◽  
E Cadherin

Numerous studies suggest that loss of E-cadherin is necessary to induce Epithelial–mesenchymal transition (EMT) and metastasis. Snail is a major contributor to EMTs. The Snail family of zinc-finger transcription factors interact with the E-cadherin promoter to repress transcription during EMT. The present article reviews the regulation of E-cadherin and discusses recent novel insights into the molecular basis in the process of EMT.

scholarly journals Long noncoding RNA AOC4P regulates tumor cell proliferation and invasion by epithelial–mesenchymal transition in gastric cancer

2019 ◽  
Vol 12 ◽  
pp. 175628481982769 ◽  
Author(s):  
Kecheng Zhang ◽  
Canrong Lu ◽  
Xiaohui Huang ◽  
Jianxin Cui ◽  
Jiyang Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Tumor Cell ◽  
Epithelial Mesenchymal Transition ◽  
Negative Control ◽  
Tumor Cell Proliferation ◽  
Mesenchymal Transition ◽  
E Cadherin

Background: The clinical relevance and biological role of tissular AOC4P in gastric cancer (GC) remains to be clarified. Methods: The association between AOC4P expression and clinicopathological characteristics was investigated. In vitro, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, wound healing and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays were performed to explore the biological effects of AOC4P on GC cell proliferation, migration, invasion, and apoptosis in MGC-803 and BGC-823 cell lines. In vivo, animal experiments were conducted to confirm the in vitro findings. Quantitative real-time polymerase chain reaction, western blotting, and immunofluorescence were used to investigate the potential mechanisms. Results: Expression levels of AOC4P were significantly higher in tumor tissues than in noncancerous tissues, and patients with high levels of AOC4P had poor overall and disease-free survival. AOC4P expression was correlated with lymphovascular invasion. In vitro, knockdown of AOC4P inhibited tumor cell proliferation, migration, and invasion, and promoted apoptosis of MGC-803 and BGC-823 cells. In vivo, BGC-823 cells transfected with AOC4P siRNA formed smaller and lighter tumors than BGC-823 cells transfected with negative control siRNA in severe combined immunodeficiency mice. Additionally, the si- AOC4P group had less proliferating cells and more apoptotic cells in tumor xenografts compared with the negative control. Mechanistically, knockdown of AOC4P decreased the expression of vimentin and MMP9, while increasing the expression of E-cadherin. Immunofluorescence confirmed the relationship between AOC4P expression and E-cadherin, vimentin, and MMP9 levels in clinical GC specimens. Conclusions: AOC4P promotes tumorigenesis and progression partly through epithelial–mesenchymal transition in GC. Additionally, AOC4P may serve as a prognostic biomarker for clinical decision making.

Sign in / Sign up

Export Citation Format

Share Document