Epithelial-mesenchymal transdifferentiation and extracellular matrix gene expression in pleomorphic adenomas of the parotid salivary gland

Aigner, Thomas; Neureiter, Daniel; Völker, Uwe; Belke, J; Kirchner, Thomas

doi:10.1002/(sici)1096-9896(1998100)186:2<178::aid-path161>3.0.co;2-2

Cited by 43 publications

(37 citation statements)

References 23 publications

(33 reference statements)

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“…Jeffrey and coworkers 8 even doubted that there exists any cartilaginous differentiation at all in chordomas and others considered chondroid chordoma as low-grade chondrosarcomas. 4,6,8,22 In the present article, using a combination of morphological features, the cytoprotein profile, and the matrix gene expression pattern as three independent and complementary tools to identify cell and tissue differentiation, 17 we could show that all of the described features of classic or chondroid chordomas are within the spectrum of the developmental differentiation pathway from the chorda dorsalis into the nucleus pulposus. This was indicated by morphology and the cytoprotein profile of the cells as outlined above.…”

Section: Discussionmentioning

confidence: 66%

“…in pleomorphic adenomas extensive cartilaginous differentiation can occur, 17 but still no chondroma-like pleomorphic adenoma of the parotid was described in the literature despite the frequency of this neoplasm. Instead, chondroid differentiation is always focal within these tumors and most likely also in chordoma.…”

Section: Discussionmentioning

confidence: 99%

“…17 As negative control for immunohistochemical stainings, the primary antibody in control sections was replaced by nonimmune mouse or rabbit serum (BioGenex, San Ramon, CA) or Tris-buffered saline (pH 7.2). None of the negative controls showed any signal.…”

Section: Immunohistochemistrymentioning

confidence: 99%

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Matrix Gene Expression Analysis and Cellular Phenotyping in Chordoma Reveals Focal Differentiation Pattern of Neoplastic Cells Mimicking Nucleus Pulposus Development

Gottschalk

Fehn

Patt³

et al. 2001

The American Journal of Pathology

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Chordoma is the fourth most common malignant primary neoplasm of the skeleton and almost the only one showing a real epithelial phenotype. Besides classic chordoma, so-called chondroid chordoma was described as a specific entity showing cartilage-like tissue within chordomatoid structures. However, since its first description, strongly conflicting results have been reported about the existence of chondroid chordoma and several studies suggested chondroid chordomas being in fact low-grade conventional chondrosarcomas. In the present study, we used cytoprotein expression profiling and molecular in situ localization techniques of marker gene products indicative of developmental phenotypes of chondrocytes to elucidate origin and biology of chondroid chordoma. We were able to demonstrate the chondrogenic potential of chordomas irrespectively of the appearance of overt cartilage formation by identifying the multifocal expression of type II collagen, the main marker of chondrocytic differentiation. Additionally, the cartilage-typical large aggregating proteoglycan aggrecan was present throughout all chordomas and, thus, a very characteristic gene product and marker of these neoplasms. Biochemical matrix composition and cell differentiation pattern analysis showed a high resemblance of classic chordomas and in chordoid areas of chondroid chordomas to the fetal chorda dorsalis, whereas chondroid areas of chondroid chordomas showed features similar to adult nucleus pulposus. This demonstrates on the cell function level the chon-

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Section: Discussionmentioning

confidence: 66%

Section: Discussionmentioning

confidence: 99%

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Matrix Gene Expression Analysis and Cellular Phenotyping in Chordoma Reveals Focal Differentiation Pattern of Neoplastic Cells Mimicking Nucleus Pulposus Development

Gottschalk

Fehn

Patt³

et al. 2001

The American Journal of Pathology

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“…Immunohistochemical and in situ hybridization studies have shown the production of aggrecan and type II collagen, extracellular matrix (ECM) substances specific to cartilage, in the myxoid and chondroid tissues. [6][7][8][9] As aggrecan is also produced in the epithelial component, 6,9 epithelial cells of pleomorphic adenoma could conceivably become chondrogenic and produce mesenchymal tissues similar to cartilage.…”

mentioning

confidence: 99%

Transcription factors related to chondrogenesis in pleomorphic adenoma of the salivary gland: a mechanism of mesenchymal tissue formation

Matsumoto

Sato

Maeda

et al. 2016

Laboratory Investigation

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In salivary gland pleomorphic adenoma, expression of extracellular matrix (ECM) substances indicates that tumor epithelial cells are becoming chondrogenic and will produce cartilage-like mesenchymal tissues. Sox9, the master transcription factor of chondrogenesis, is expressed in mouse salivary gland cells. To clarify the mechanism behind chondrogenesis in tumor epithelial cells, we examined the expression of transcription factors related to chondrogenesis in tumors and salivary glands. Reverse transcriptase-polymerase chain reaction (RT-PCR), quantitative real-time RT-PCR, and immunostaining were performed on pleomorphic adenoma tissues, salivary gland tissues, and human submandibular gland (HSG) cells. The mRNAs of essential transcription factors for chondrogenesis-Sox9, Sox6, and Sox5-were detected in both tumor and salivary gland tissues. The mRNAs of aggrecan and type II collagen-cartilage-specific ECM substances-were detected only in tumors. Sox9 and Sox6 proteins were colocalized in many epithelial cells in tumors and salivary glands. Tumor epithelial cells also possessed aggrecan protein and occasionally type II collagen protein. Moreover, mRNAs for transcription repressors of chondrogenesis δEF1 and AP-2α were detected in both tumors and salivary glands, whereas Twist1 mRNA was detected only in salivary glands and was at significantly low-to-undetectable levels in tumors. Twist1 protein was localized in the Sox9-expressing salivary gland cells. HSG cells expressed Sox9, Sox6, and Twist1, but not aggrecan or type II collagen, and thus were similar to salivary gland cells. Twist1 depletion by Twist1 siRNA led to the upregulation of aggrecan and type II collagen mRNA expression in HSG cells. In contrast, forced expression of Twist1, using Twist1 cDNA, resulted in the downregulation of both these genes. Taken together, these results indicate that salivary gland cells have a potential for chondrogenesis, and Twist1 depletion concomitant with neoplastic transformation, which would permit tumor epithelial cells to produce cartilage-like mesenchymal tissues in salivary gland pleomorphic adenoma. (2016) 96, 16-24; doi:10.1038/labinvest.2015 published online 26 October 2015 Pleomorphic adenoma is the most common tumor of the salivary gland. It is characterized by mixed appearance of epithelial and mesenchymal components. 1,2 A number of ultrastructural and immunohistochemical studies have shown that the mesenchymal component (typically composed of myxoid and chondroid tissues) is epithelial in origin (e.g., Dardick et al. 3,4 and Erlandson et al. 5 ). Immunohistochemical and in situ hybridization studies have shown the production of aggrecan and type II collagen, extracellular matrix (ECM) substances specific to cartilage, in the myxoid and chondroid tissues. [6][7][8][9] As aggrecan is also produced in the epithelial component, 6,9 epithelial cells of pleomorphic adenoma could conceivably become chondrogenic and produce mesenchymal tissues similar to cartilage. Laboratory InvestigationWhen forced to express ...

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“…In the pleomorphic adenomas case, the detection (by in situ hybridization technique) in the ductal cells of the genes involved in the aggregan core protein mRNA synthesis, has demonstrated the expression of the mesenchymal genes in the cells with epithelial origin [23]. Thus, the onset of the mesenchymal gene expression in the ductal cells leads to the secretion of an abundant extracellular matrix rich in glycosaminoglycan that generates the myxoid matrix formation.…”

Section: Discussionmentioning

confidence: 99%

The ultrastructural aspects of neoplastic myoepithelial cell in pleomorphic adenomas of salivary glands

Mărgăritescu¹,

Raica²,

Florescu³

et al. 2004

J Cellular Molecular Medi

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The salivary gland pleomorphic adenoma is a benign epithelial neoplasm, histologically characterized by a great diversity of morphological aspects. According to literature data, the pleomorphic adenoma represents 45-74 % of all the salivary gland tumors [1][2][3][4]. At the Armed Forces Institute of Pathology (AFIP) the pleomorphic adenomas represent 60 % of the benign tumors from all the salivary gland sites: 61 % of the major gland tumors and 54 % of the minor gland tumors [5]. AbstractThe purpose of this study has been to establish the major ultrastructural aspects of the myoepithelial cell and the myoepithelial-like cells proliferated in the pleomorphic adenomas of salivary glands. Thus, twelve benign pleomorphic adenomas of salivary glands have been studied by electron-microscopy transmission techniques. Our analysis has proved the proliferation of two major cellular populations, one of ductal type and one of myoepithelial type, which tried to reproduce the tubulo-acinar cytoarchitecture from the normal salivary glands. We have also noticed the key role of the so-called 'modified' myoepithelial cells from the periphery of the proliferating epithelial units in the genesis of the myxoid and chondromyxoid tumoral stromal areas. All these ultrastructural aspects have explained the great histological diversity of these salivary gland neoplasms as well as the key role of the myoepithelial cell in its histogenesis.

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Epithelial-mesenchymal transdifferentiation and extracellular matrix gene expression in pleomorphic adenomas of the parotid salivary gland

Cited by 43 publications

References 23 publications

Matrix Gene Expression Analysis and Cellular Phenotyping in Chordoma Reveals Focal Differentiation Pattern of Neoplastic Cells Mimicking Nucleus Pulposus Development

Matrix Gene Expression Analysis and Cellular Phenotyping in Chordoma Reveals Focal Differentiation Pattern of Neoplastic Cells Mimicking Nucleus Pulposus Development

Transcription factors related to chondrogenesis in pleomorphic adenoma of the salivary gland: a mechanism of mesenchymal tissue formation

The ultrastructural aspects of neoplastic myoepithelial cell in pleomorphic adenomas of salivary glands

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