Dexamethasone resets stable association of nuclear Snail with LSD1 concomitant with transition from EMT to partial EMT.

Cancer cells utilize epithelial to mesenchymal transition (EMT) during invasion and metastasis. This program has intermediate cell states with retained epithelial and gained mesenchymal features together, referred to as partial EMT. Histone demethylase LSD1 forms a complex with the EMT master transcription factor Snail to modify histone marks and regulate target gene expression.

The squamous cell carcinoma cell line OM-1 retains both p75-dependent stratified epithelial progenitor potential and cancer stem cell properties.

The low-affinity nerve growth factor receptor p75 is a stratified epithelial stem/progenitor marker of human epithelia. We found OM-1, a human squamous cell carcinoma (SCC) cell line, showed distinct cells with p75 cluster, especially located at the center of a growing colony in a monolayer culture. A cell with p75 cluster was surrounded by cytokeratin 14- and cytokeratin 13-expressing cells that settled at the outer margin of the colony.

TGF-β1 induces amoeboid-to-mesenchymal transition of CD44 oral squamous cell carcinoma cells via miR-422a downregulation through ERK activation and Cofilin-1 phosphorylation.

Background: The objective of this study was to clarify the molecular mechanism of amoeboid-to-mesenchymal transition (AMT) of CD44 oral squamous cell carcinoma (OSCC) cells.

Methods: Morphology and expression of mesenchymal genes were investigated in CD44 OSCC cells (CD44 OM-1 cells) cultured on laminin-coated soft silicone gel. Additionally, microarray analysis was performed to investigate microRNA (miRNA) expression inhibited by transforming growth factor-β1 (TGF-β1) in CD44 OM-1 cells.

Effect of hydrogel stiffness on morphology and gene expression pattern of CD44 oral squamous cell carcinoma cells.

The stiffness of extracellular matrix (ECM) has been associated with tumor growth, phenotypic plasticity, and invasion through modulation of the intracellular signaling pathway. However, the effect of ECM stiffness on oral cancer stem cells (CSCs) has not been fully elucidated. Therefore, we preliminarily investigated changes in phenotype and gene expression in CD44 positive-oral squamous cell carcinoma (OSCC) cells (i.

Preoperative oral health care reduces postoperative inflammation and complications in oral cancer patients.

The records of 70 patients with oral cancer who were treated at a single institution between 2008 and 2014 were reviewed. The body temperature, white blood cell count, and C-reactive protein (CRP) levels were compared between those who had received preoperative oral care (oral care group) and those who had not received any (non-oral care group). When the patients were divided into those who underwent minimally invasive surgery and those who underwent severely invasive surgery, the mean CRP level in the early postoperative period was lower in the oral care group as compared with the non-oral care group in those who underwent minimally invasive surgery as well as those who underwent severely invasive surgery.

CD44(high) /ALDH1(high) head and neck squamous cell carcinoma cells exhibit mesenchymal characteristics and GSK3β-dependent cancer stem cell properties.

Background: CD44 and aldehyde dehydrogenase 1 (ALDH1) have been shown to be useful markers for identification of cancer stem cells (CSCs). We previously reported that glycogen synthase kinase 3β (GSK3β) is involved in regulation of the self-renewal ability of head and neck squamous cell carcinoma (HNSCC) CSCs. The purpose of the present study was to clarify the role of GSK3β in CD44(high) /ALDH1(high) HNSCC cells.

Clinicopathological analysis of salivary gland carcinomas and literature review.

Malignant salivary gland tumors are rare and exhibit a broad spectrum of phenotypic heterogeneity. The objective of this study was to investigate prognostic factors in patients with salivary gland carcinomas and review the results in light of other reports. We retrospectively reviewed 40 patients with primary salivary gland carcinomas who were diagnosed and treated at our institution between 1991 and 2014.

Role of receptor for hyaluronan-mediated motility (RHAMM) in human head and neck cancers.

The receptor for hyaluronan (HA)-mediated motility (RHAMM) is a HA-binding protein located in the cytoskeleton and centrosome. RHAMM has multiple functions that manifest with different cellular localizations, for example, modulation of growth factor receptor, regulation of cell signaling pathways, and mitotic spindle assembly. In addition, its increased expression has major roles in tumorigenesis and can induce genomic instability and cancer progression.

Autocrine galectin-1 promotes collective cell migration of squamous cell carcinoma cells through up-regulation of distinct integrins.

We found that high galectin-1 (Gal-1) mRNA levels were associated with invasive squamous cell carcinoma (SCC) cells that expressed Snail, an epithelial-to-mesenchymal transition (EMT) regulator. Both Gal-1 overexpression and soluble Gal-1 treatment accelerated invasion and collective cell migration, along with activation of cdc42 and Rac. Soluble Gal-1 activated c-Jun N-terminal kinase to increase expression levels of integrins α2 and β5, which were essential for Gal-1 dependent collective cell migration and invasiveness.

AKT primes snail-induced EMT concomitantly with the collective migration of squamous cell carcinoma cells.

In this study, we found that wounding of a confluent monolayer of squamous cell carcinoma (SCC) cells induced epithelial-mesenchymal transition (EMT) specifically at the edge of the wound. This process required the combined stimulation of TGFβ, TNFα, and PDGF-D. Such a combined cytokine treatment of confluent monolayers of the cells upregulated the expression levels of Snail and Slug via PI3K.

Expression of receptor for hyaluronan-mediated motility (RHAMM) in ossifying fibromas.

Fibro-osseous lesions of the jaw are poorly understood because of a significant overlap of clinical, radiological and histological features among the various types, though they present distinct patterns of disease progression. An ossifying fibroma is associated with significant cosmetic and functional disturbances, as it shows expansive proliferation. Thus, it is important to establish a specific marker, as well as clearly elucidate its etiology for diagnosis and proper treatment.

Snail promotes Cyr61 secretion to prime collective cell migration and form invasive tumor nests in squamous cell carcinoma.

We previously identified genes associated with Snail-mediated squamous cell carcinoma (SCC) invasiveness, in which we observed significant elevation of Cyr61 expression. In this study, SCC cell lines overexpressing Cyr61 exhibited constitutive activation of Rho A and upregulated invasiveness without the disruption of homophilic cell attachment. Humoral Cyr61 enhanced further production of endogenous Cyr61 by SCC cells, which stimulated collective cell migration and the development of an invasive tumor nest.

Overexpression of receptor for hyaluronan-mediated motility (RHAMM) in MC3T3-E1 cells induces proliferation and differentiation through phosphorylation of ERK1/2.

Receptor for hyaluronan (HA)-mediated motility (RHAMM) was first described as a soluble HA binding protein released by sub-confluent migrating cells. We previously found that RHAMM was highly expressed and plays an important role in proliferation in the human cementifying fibroma (HCF) cell line, which we previously established. HCF is a benign fibro-osseous neoplasm of the jaw and is composed of fibrous tissue containing varying amounts of mineralized material.

PGE₂ targets squamous cell carcinoma cell with the activated epidermal growth factor receptor family for survival against 5-fluorouracil through NR4A2 induction.

We found a linear correlation between the Prostaglandin E(2) (PGE(2)) amount and the NR4A2 expression in oral squamous cell carcinoma (SCC) tissues through a statistical analysis among 41 clinical cases. In SCC cell lines, PGE(2) receptor (EP) ligation by exogenous PGE(2) promoted the NR4A2 expression in the cAMP/protein kinase A (PKA)-dependent manner. The process required a nature of SCC cell represented by constitutive activated epidermal growth factor receptor (EGFR) family.

RHAMM/ERK interaction induces proliferative activities of cementifying fibroma cells through a mechanism based on the CD44-EGFR.

We have previously established immortalized cells (HCF) from cementifying fibroma of the jaw bone. Here, we found that the receptor for hyaluronan (HA)-mediated motility (RHAMM) and epiregulin, a ligand for the epidermal growth factor receptor (EGFR), were highly expressed in HCF cells in comparison with osteoblasts by conducting a microarray analysis. The cell growth of HCF cells was significantly decreased by the knockdown of RHAMM using small interfering RNA (siRNA).

Nodal lymphangiogenesis and metastasis: Role of tumor-induced lymphatic vessel activation in extramammary Paget's disease.

Nodal lymphangiogenesis promotes distant lymph node (LN) metastasis in experimental cancer models. However, the role of nodal lymphangiogenesis in distant metastasis and in the overall survival of cancer patients remains unknown. Therefore, we investigated mechanisms that might facilitate regional and distant LN metastasis in extramammary Paget's disease (EMPD).

Overexpression of the receptor for hyaluronan-mediated motility, correlates with expression of microtubule-associated protein in human oral squamous cell carcinomas.

Receptor for hyaluronan-mediated motility (RHAMM) has previously been characterized as a cell surface receptor for hyaluronan and a microtubule-associated intracellular hyaluronan binding protein. We examined the expression of RHAMM mRNA in 43 oral squamous cell carcinomas (SCCs) and 7 normal gingivae by real-time RT-PCR. The expression level of RHAMM mRNA was significantly higher in oral SCCs than normal gingivae (P=0.

DeltaNp63alpha-dependent expression of Id-3 distinctively suppresses the invasiveness of human squamous cell carcinoma.

p63 is a member of the p53 family and DeltaNp63alpha is the dominant-expressing isoform of p63 in basal layer of normal stratified epithelium and human squamous cell carcinoma (SCC) cells. We have previously reported that down-regulation of p63 was accompanied with epithelial-to-mesenchymal transition (EMT) by Snail-expressing SCC cells, in which re-expression of DeltaNp63alpha diminished their invasiveness (Higashikawa K, Yoneda S, Tobiume K, Taki M, Shigeishi H, Kamata N. Snail-induced down-regulation of DeltaNp63alpha acquires invasive phenotype of human squamous cell carcinoma.

Expression of TPX2 in salivary gland carcinomas.

TPX2 is a microtubule-associated protein and is required for microtubule formation at kinetochores in mammalian cells. The purpose of this study was to clarify the expression of TPX2 mRNA and correlation between TPX2 and clinicopathological factors in salivary gland carcinomas. The expression of TPX2 mRNA was investigated in 20 human salivary gland carcinomas (8 mucoepidermoid carcinomas, 7 adenoid cystic carcinomas, 5 acinic cell carcinomas) and 6 normal submandibular glands using real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR).

Expression of epiregulin, a novel epidermal growth factor ligand associated with prognosis in human oral squamous cell carcinomas.

We examined the expression of epiregulin and amphiregulin mRNA in 39 oral SCCs, 2 epithelial dysplasias and 7 normal gingivae by real-time RT-PCR. The mean expression level of epiregulin mRNA was higher in oral SCCs (0.29+/-0.

Up-regulation of stromal cell-derived factor-1alpha and its receptor CXCR4 expression accompanied with epithelial-mesenchymal transition in human oral squamous cell carcinoma.

Stromal cell-derived factor 1alpha (SDF-1alpha) and its receptor CXCR4 have been implicated in the tumorigenesis, proliferation, and lymph node metastasis of cancer. Here, we report that highly invasive squamous cell carcinoma (SCC) cells with a spindle cell morphology show a strong expression of both SDF-1alpha and CXCR4. CXCR4 expression and cell migratory activity were further up-regulated by treatment with SDF-1alpha or TGF-beta1 in these cells.

Gene expression profiling to identify genes associated with high-invasiveness in human squamous cell carcinoma with epithelial-to-mesenchymal transition.

The process of epithelial-to-mesenchymal transition (EMT) involves the acquisition of high-invasiveness by tumor. Snail represses target genes and induces EMT. In this study, we defined the signatures of gene expressions by cDNA microarray analyses in both human squamous cell carcinoma (SCC) cell lines with spontaneous EMT and with Snail-induced EMT, which exhibited high-invasive behavior in vitro.

Snail-induced down-regulation of DeltaNp63alpha acquires invasive phenotype of human squamous cell carcinoma.

p63 is a member of the p53 family and regulates crucial events in the formation of epithelial structures, but the role of p63 in tumor is unclear. We found that Snail-induced epithelial-to-mesenchymal transition (EMT) is accompanied by down-regulation of p63 in human squamous cell carcinomas (SCC). DeltaNp63alpha is the predominantly expressed p63 isoform in SCC cells.

Concrescence of teeth: cemental union between the crown of an impacted tooth and the roots of an erupted tooth.

Concrescence of teeth is a condition showing a union of adjacent teeth by only cementum. In all the previously reported cases, the union has been observed between the roots of the affected teeth. Here, we describe the first case that showed a concrescence of the crown of an impacted tooth and the roots of the erupted tooth.