scholarly journals Investigation of the Epithelial to Mesenchymal Transition (EMT) Process in Equine Papillomavirus-2 (EcPV-2)-Positive Penile Squamous Cell Carcinomas

2021 ◽  
Vol 22 (19) ◽  
pp. 10588
Author(s):  
Federico Armando ◽  
Samanta Mecocci ◽  
Virginia Orlandi ◽  
Ilaria Porcellato ◽  
Katia Cappelli ◽  
...  

Equine penile squamous cell carcinoma (epSCC) is the most frequent tumor of the external male genitalia, representing 67.5% of equine genital cancers. epSCC is associated with papilloma virus (PV) infection and has been recently proposed as a model for human PV-induced squamous cell carcinomas. It has already been suggested that epSCC might undergo epithelial-to-mesenchymal transition (EMT). This work aims to investigate in detail this process and the possible role of PV oncoproteins in epSCC. For this purpose, 18 penile SCCs were retrospectively selected and tested for both EcPV2 presence and oncoproteins (EcPV2 E6 and EcPV2 E7) expression. Moreover, immunohistochemical EMT characterization was carried out by analyzing the main epithelial markers (E-cadherin, β-catenin, and pan-cytokeratin AE3/AE1), the main mesenchymal markers (N-cadherin and vimentin), and the main EMT-related transcription factors (TWIST-1, ZEB-1). PCR analysis was positive for EcPV2 in 16 out of 18 samples. EMT was investigated in epSCC positive for EcPV2. The immunohistochemistry results suggested the presence of EMT processes in the neoplastic cells at the tumor invasive front. Moreover, the significant upregulation of RANKL, together with BCATN1, LEF1, and FOSL1 genes, might suggest a canonical Wnt pathway activation, similarly to what is reported in human penile squamous cell carcinomas

Animals ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 2318
Author(s):  
Federico Armando ◽  
Francesco Godizzi ◽  
Elisabetta Razzuoli ◽  
Fabio Leonardi ◽  
Mario Angelone ◽  
...  

Squamous cell carcinoma (SCC) is one of the most frequent tumors of skin and muco-cutaneous junctions in the horse. Equine papillomavirus type 2 (EcPV2) has been detected in equine SCC of the oral tract and genitals, and recently also in the larynx. As human squamous cell carcinoma of the larynx (SCCL), it is strongly etiologically associated with high-risk papillomavirus (h-HPV) infection. This study focuses on tumor cells behavior in a naturally occurring tumor that can undergo the so-called epithelial to mesenchymal transition (EMT). A SCCL in a horse was investigated by immunohistochemistry using antibodies against E-cadherin, pan-cytokeratin AE3/AE1, β-catenin, N-cadherin, vimentin, ZEB-1, TWIST, and HIF-1α. EcPV2 DNA detection and expression of oncogenes in SCC were investigated. A cadherin switch and an intermediate filaments rearrangement within primary site tumor cells together with the expression of the EMT-related transcription factors TWIST-1, ZEB-1, and HIF-1α were observed. DNA obtained from the tumor showed EcPV2 positivity, with E2 gene disruption and E6 gene dysregulation. The results suggest that equine SCCL might be a valuable model for studying EMT and the potential interactions between EcPV2 oncoproteins and the EMT process in SCCL.


2017 ◽  
Vol 33 (1) ◽  
pp. 73-78 ◽  
Author(s):  
Xiaoxia Wang ◽  
Chun He ◽  
Chaohui Li ◽  
Benhong Ren ◽  
Qing Deng ◽  
...  

Background: Laryngeal squamous cell carcinoma (LSCC) has a poor prognosis due to recurrence and metastasis. IQ-domain GTPase-activating protein 1 (IQGAP1), a scaffold protein, plays an important role in tumorigenesis and malignant development. In this study, we aimed to explore the role of IQGAP1 in LSCC. Methods: Expression of IQGAP1 in human LSCC specimens was assessed by immunohistochemistry. We also evaluated the roles of IQGAP1 in cell proliferation, migration and invasion and epithelial-to-mesenchymal transition (EMT) in Hep-2 cells. Results: The expression of IQGAP1 protein was significantly up-regulated in LSCC tissues compared with normal laryngeal tissues (p = 0.002). Furthermore, the knockdown of IQGAP1 in Hep-2 cells inhibited cell growth, migration and invasion. Moreover, we found that IQGAP1 silencing reversed EMT. Conclusions: These results show for the first time that IQGAP1 is up-regulated in LSCC tissues and plays an important role in LSCC cell proliferation and invasiveness, which indicates that IQGAP1 could work as an oncogene and may serve as a promising molecular target for treatment of LSCC.


2020 ◽  
Vol 145 ◽  
pp. 110346
Author(s):  
Thodur Madapusi Balaji ◽  
Saranya Varadarajan ◽  
Raghunathan Jagannathan ◽  
A. Thirumal Raj ◽  
Lakshmi Priya Sridhar ◽  
...  

2019 ◽  
Vol 2 (2) ◽  
Author(s):  
Andreea Calinescu ◽  
Cristian Scheau ◽  
Sabina Zurac ◽  
Roxana Ioana Nedelcu ◽  
Alice Brinzea ◽  
...  

E-cadherin is an adhesion molecule essential in maintaining cellular integrity and preserving normal epithelial tissue architecture in adult organisms. Loss of E-cadherin expression and epithelial characteristics has been described in the late stages of carcinogenesis in various human cancers. By loosing cell-cell adhesion mediated by E-cadherin and acquiring mesenchymal properties, a process reffered to as epithelial to mesenchymal transition (EMT), carcinoma cells become more motile and invasive, thus being able to penetrate the surrounding stroma. Our aim is to investigate E-cadherin expression, part of the EMT phenomenom, in cutaneous squamous cell carcinomas (cSCCs), knowing that it represents a valuable model for understanding cancer progression. We conducted a retrospective study, performing immunohistochemical staining of E-cadherin and analyzing its expression in 32 cases of primary cSCCs. E-cadherin membrane positivity was assessed in cells from the main tumor and cells from the invasion front and described in terms of percentage of positive tumoral cells and in terms of intensity. Statistycal analysis showed the proportion of E-Cadherin positive cells in the tumor central and superficial areas is lower in higher degrees of anaplasia (marginally significant p=0.07), confirming the higher potential of poor outcome in these tumors. Median intensity and proportion values of E-Cadherin positive cells were significantly higher in the tumor central and superficial areas than in the invasion front (p<0.0001), suggesting that loss of epithelial features portends higher potential of invasion and metastasis in the setting of EMT. Further studies are required in order to establish clear correlations.


2015 ◽  
Vol 193 (2) ◽  
pp. 699-705 ◽  
Author(s):  
Emili Masferrer ◽  
Carla Ferrándiz-Pulido ◽  
Magalí Masferrer-Niubò ◽  
Alfredo Rodríguez-Rodríguez ◽  
Inmaculada Gil ◽  
...  

2018 ◽  
Author(s):  
Silvia Crespo Pomar ◽  
Anna Borgström ◽  
Alexandre Arcaro ◽  
Roch-Philippe Charles

AbstractWhile the class I of PI3Ks has been deeply studied due to its clear implication in cancer development, little is known about the class II of PI3Ks. However, recent accumulation of data is now revealing that PI3KC2β, one isoform of this class of PI3Ks, may also play a role in cancer. Specifically, recent studies have suggested an implication of PI3KC2β in metastasis formation through the promotion of epithelial to mesenchymal transition (EMT). Here, we report that the overexpression of PI3KC2β in the epidermal squamous cell carcinoma (ESCC) cells A431 promotes apparent EMT transformation. We further confirm this EMT by showing modification in several biochemical markers (E-cadherin, β-catenin, Snail, Twist1 and Vimentin). Furthermore, an intracellular co-localization of E-cadherin, β-catenin and EGFR was observed. This transformation decreased EGFR signaling and the sensitivity to inhibitors targeting this receptor. To confirm our results, we have used the colon adenocarcinoma cells HT29 and induced overexpression of PI3KC2β in these cells. We could recapitulate in this model some of our major findings regarding EMT in the PI3KC2β overexpressing A431 cells. Taken together, these data support a role of PI3KC2β in promoting EMT.


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