Epithelial to Mesenchymal Transition in Clear Cell Renal Cell Carcinoma with Rhabdoid Features

Abstract

Aims: The aims of this study were to investigate the association of renal cell carcinoma (RCC) displaying rhabdoid features and morphologically mesenchymal characteristics with epithelial to mesenchymal transition (EMT), and to clarify the expression of EMT markers. Methods: We investigated the expression of EMT markers (E-cadherin, vimentin, Snail, Slug, ZEB1, ZEB2 and Twist1) using immunohistochemistry, Western blotting and real-time polymerase chain reaction in 18 cases of clear cell RCC (ccRCC) with rhabdoid features and 74 ccRCC cases with Fuhrman grade 1-3 (G1 to G3). Results: In ccRCCs with rhabdoid features, low E-cadherin and high vimentin expression were found. In G1 to G3 ccRCCs, low E-cadherin expression and high expression of vimentin, ZEB1 and ZEB2 were found. There was no significant difference in the immunoexpression of E-cadherin and vimentin between the two ccRCC groups. Conclusions: The rhabdoid features may histologically and biologically be associated with EMT in ccRCC. There is a possibility that in G1 to G3 ccRCCs showing epithelial structures, other cell-cell adhesion mechanisms apart from E-cadherin adhesion may continue to work, and that ccRCC with rhabdoid features may be caused by an inactivation or loss of these mechanisms.

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“…Loss of epithelial cell characteristics makes it difficult for cells to adhere, and the acquisition of interstitial cell characteristics makes it easier for cells to metastasize. 18 Numerous molecular alternations occur in the process of EMT, such as the loss or low E-cadherin Figure 3 CSE can activate the ERK5/AP-1 signaling pathway. (A) t-ERK5, -fos and -jun levels were notably decreased depending on the CSE dose.…”

“…Loss of epithelial cell characteristics makes it difficult for cells to adhere, and the acquisition of interstitial cell characteristics makes it easier for cells to metastasize. 18 Numerous molecular alternations occur in the process of EMT, such as the loss or low E-cadherin expression as well as the up-regulated N-cadherin expression, referred to as “cadherin switch”, which is typically observed during EMT via the interruption of tight junctions and the concomitant gain of cell motility. In vitro IHC had been carried out to evaluate levels of N-cadherin, E-cadherin, Vimentin, as well as ZO-1 EMT markers in RCC specimens, proving that they correlated with the prognosis of patients with RCC.…”

“…In vitro IHC had been carried out to evaluate levels of N-cadherin, E-cadherin, Vimentin, as well as ZO-1 EMT markers in RCC specimens, proving that they correlated with the prognosis of patients with RCC. 18 , 19 Yu et al demonstrated that EMT caused epithelial cells to significantly change their cell morphology, and increase their proliferation and invasion in human normal bladder epithelial cells and mouse models. 9 Giordano et al 20 found that EMT-inducing factors not only induced the occurrence of EMT in breast cancer cells but also enhance their stem cell characteristics.…”

Zinc finger E‑box binding homeobox�2 functions as an oncogene in human laryngeal squamous cell carcinoma

“…Mounting evidence has indicated that ZEB2 is involved in the initiation and development of malignancies (8). Furthermore, it has been reported that ZEB2 promotes the epithelial-mesenchymal transition (EMT), a pathological process leading to specific morphological and phenotypic alterations during cancer metastasis in tumor cells (9,10). According to previous studies, ZEB2 was significantly upregulated in LSCC (11,12).…”

Clinicopathological Significance and Antitumor Effect of MPHOSPH1 in Testicular Germ Cell Tumor

“…The membranes were then incubated overnight at 4°C with secondary antibodies. The bound antibody was visualized using an ECL kit (GE Healthcare Bio-Sciences) and the membranes were exposed to X-ray film (GE Healthcare Bio-Sciences) 18 - 20 . The protein levels were standardized by actin using an image analyzer (Ez-Capture MG; ATTO, Tokyo), and the expression signal relative to the standardized signal was regarded as the level of expression for each sample.…”