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Scientific Reports Jan 2024Salivary gland myoepithelial cells regulate saliva secretion and have been implicated in the histological diversity of salivary gland tumors. However, detailed...
Salivary gland myoepithelial cells regulate saliva secretion and have been implicated in the histological diversity of salivary gland tumors. However, detailed functional analysis of myoepithelial cells has not been determined owing to the few of the specific marker to isolate them. We isolated myoepithelial cells from the submandibular glands of adult mice using the epithelial marker EpCAM and the cell adhesion molecule CD49f as indicators and found predominant expression of the transcription factor FoxO1 in these cells. RNA-sequence analysis revealed that the expression of cell cycle regulators was negatively regulated in FoxO1-overexpressing cells. Chromatin immunoprecipitation analysis showed that FoxO1 bound to the p21/p27 promoter DNA, indicating that FoxO1 suppresses cell proliferation through these factors. In addition, FoxO1 induced the expression of ectodysplasin A (Eda) and its receptor Eda2r, which are known to be associated with X-linked hypohidrotic ectodermal dysplasia and are involved in salivary gland development in myoepithelial cells. FoxO1 inhibitors suppressed Eda/Eda2r expression and salivary gland development in primordial organ cultures after mesenchymal removal. Although mesenchymal cells are considered a source of Eda, myoepithelial cells might be one of the resources of Eda. These results suggest that FoxO1 regulates myoepithelial cell proliferation and Eda secretion during salivary gland development in myoepithelial cells.
Topics: Animals; Mice; Ectodysplasins; Epithelial Cells; Receptors, Tumor Necrosis Factor; Salivary Gland Neoplasms; Submandibular Gland; Transcription Factors; Xedar Receptor
PubMed: 38212454
DOI: 10.1038/s41598-024-51619-1 -
Journal of Dental Research Oct 2019Maintaining salivary gland function is critical for oral health. Loss of saliva is a common side effect of therapeutic irradiation for head and neck cancer or autoimmune... (Review)
Review
Maintaining salivary gland function is critical for oral health. Loss of saliva is a common side effect of therapeutic irradiation for head and neck cancer or autoimmune diseases such as Sjögren's syndrome. There is no curative treatment, and current strategies proposed for functional regeneration include gene therapy to reengineer surviving salivary gland tissue, cell-based transplant therapy, use of bioengineered glands, and development of drugs/biologics to stimulate in vivo regeneration or increase secretion. Understanding the genetic and cellular mechanisms required for development and homeostasis of adult glands is essential to the success of these proposed treatments. Recent advances in genetic lineage tracing provide insight into epithelial lineage relationships during murine salivary gland development. During early fetal gland development, epithelial cells expressing keratin 14 (K14) Sox2, Sox9, Sox10, and Trp63 give rise to all adult epithelium, but as development proceeds, lineage restriction occurs, resulting in separate lineages of myoepithelial, ductal, and acinar cells in postnatal glands. Several niche signals have been identified that regulate epithelial development and lineage restriction. Fibroblast growth factor signaling is essential for gland development, and other important factors that influence epithelial patterning and maturation include the Wnt, Hedgehog, retinoic acid, and Hippo signaling pathways. In addition, other cell types in the local microenvironment, such as endothelial and neuronal cells, can influence epithelial development. Emerging evidence also suggests that specific epithelial cells will respond to different types of salivary gland damage, depending on the cause and severity of damage and the resulting damaged microenvironment. Understanding how regeneration occurs and which cell types are affected, as well as which signaling factors drive cell lineage decisions, provides specific targets to manipulate cell fate and improve regeneration. Taken together, these recent advances in understanding cell lineages and the signaling factors that drive cell fate changes provide a guide to develop novel regenerative treatments.
Topics: Animals; Cell Lineage; Epithelial Cells; Keratins; Mice; SOX Transcription Factors; Salivary Glands; Signal Transduction; Trans-Activators
PubMed: 31331226
DOI: 10.1177/0022034519864592 -
Journal of Oral and Maxillofacial... 2016Myoepithelial cells (MECs) are considered to be a key participant in most salivary gland diseases, particularly tumors. MECs structurally resemble both epithelial cells... (Review)
Review
Myoepithelial cells (MECs) are considered to be a key participant in most salivary gland diseases, particularly tumors. MECs structurally resemble both epithelial cells and smooth muscles. Diagnostic dilemmas caused are due to inadequacy of characterizing the wide spectrum of morphologic and immunologic features which are different for both normal and neoplastic MECs. This article discusses the development, functions and structure of both normal and neoplastic MECs, their staining properties and differences in the morphologic and immunophenotypic properties of the MEC in detail. It also describes the role of MEC in pathogenesis and morphogenesis of various nonneoplastic and neoplastic salivary gland lesions and thereby are responsible for the myriad histopathology of salivary gland tumors.
PubMed: 27721615
DOI: 10.4103/0973-029X.190952 -
The Journal of Cell Biology Aug 2019In epithelial cancers, cells must invade through basement membranes (BMs) to metastasize. The BM, a thin layer of extracellular matrix underlying epithelial and... (Review)
Review
In epithelial cancers, cells must invade through basement membranes (BMs) to metastasize. The BM, a thin layer of extracellular matrix underlying epithelial and endothelial tissues, is primarily composed of laminin and collagen IV and serves as a structural barrier to cancer cell invasion, intravasation, and extravasation. BM invasion has been thought to require protease degradation since cells, which are typically on the order of 10 µm in size, are too large to squeeze through the nanometer-scale pores of the BM. However, recent studies point toward a more complex picture, with physical forces generated by cancer cells facilitating protease-independent BM invasion. Moreover, collective cell interactions, proliferation, cancer-associated fibroblasts, myoepithelial cells, and immune cells are all implicated in regulating BM invasion through physical forces. A comprehensive understanding of BM structure and mechanics and diverse modes of BM invasion may yield new strategies for blocking cancer progression and metastasis.
Topics: Animals; Basement Membrane; Biomechanical Phenomena; Cell Communication; Humans; Neoplasm Invasiveness; Neoplasms; Peptide Hydrolases
PubMed: 31315943
DOI: 10.1083/jcb.201903066 -
Head and Neck Pathology Mar 2023Optically clear cytoplasm may occur in neoplastic and non-neoplastic conditions, either as a characteristic feature of a disease entity or as a morphologic rarity,... (Review)
Review
BACKGROUND
Optically clear cytoplasm may occur in neoplastic and non-neoplastic conditions, either as a characteristic feature of a disease entity or as a morphologic rarity, potentially creating diagnostic dilemmas in various organ systems. In the head and neck, clear cell change can occur in lesions of salivary, odontogenic, thyroid, parathyroid, or sinonasal/skull base origin, as well as in metastases to these regions.
METHODS
This review elaborates the top ten clear cell lesions in the head and neck, emphasizing their distinguishing histologic, immunohistochemical, and molecular attributes, and presents a rational approach to arriving at an accurate classification.
RESULTS
Cytoplasmic pallor or clearing may be caused by accumulations of glycogen, lipid, mucin, mucopolysaccharides, water, foreign material, hydropic organelles, or immature zymogen granules. Overlapping morphologic features may present a diagnostic challenge to the surgical pathologist. Similarity in immunohistochemical profiles, often due to common cell type, as well as rare non-neoplastic mimics, furthers the diagnostic conundrum.
CONCLUSIONS
The top ten lesions reviewed in this article are as follows: (1) clear cell carcinoma (salivary and odontogenic), (2) mucoepidermoid carcinoma, (3) myoepithelial and epithelial-myoepithelial carcinoma, (4) oncocytic salivary gland lesions, (5) squamous cell carcinoma, (6) parathyroid water clear cell adenoma, (7) metastatic renal cell carcinoma (especially in comparison to clear cell thyroid neoplasms), (8) sinonasal renal cell-like adenocarcinoma, (9) chordoma, and (10) rhinoscleroma.
Topics: Humans; Carcinoma, Renal Cell; Kidney Neoplasms; Epithelial Cells; Carcinoma, Squamous Cell; Adenocarcinoma, Clear Cell; Salivary Gland Neoplasms
PubMed: 36928734
DOI: 10.1007/s12105-022-01518-6 -
Scientific Reports Jan 2022Sweat glands play an important role in thermoregulation via sweating, and protect human vitals. The reduction in sweating may increase the incidence of hyperthermia....
Sweat glands play an important role in thermoregulation via sweating, and protect human vitals. The reduction in sweating may increase the incidence of hyperthermia. Myoepithelial cells in sweat glands exhibit stemness characteristics and play a major role in sweat gland homeostasis and sweating processes. Previously, we successfully passaged primary myoepithelial cells in spheroid culture systems; however, they could not be maintained for long under in vitro conditions. No myoepithelial cell line has been established to date. In this study, we transduced two immortalizing genes into primary myoepithelial cells and developed a myoepithelial cell line. When compared with primary sweat gland cells, the immortalized myoepithelial cells (designated "iEM") continued to form spheroids after the 4th passage and expressed α-smooth muscle actin and other proteins that characterize myoepithelial cells. Furthermore, treatment with small compounds targeting the Wnt signaling pathways induced differentiation of iEM cells into luminal cells. Thus, we successfully developed an immortalized myoepithelial cell line having differentiation potential. As animal models are not useful for studying human sweat glands, our cell line will be helpful for studying the mechanisms underlying the pathophysiology of sweating disorders.
Topics: Actins; Cell Differentiation; Cell Line, Transformed; Cells, Cultured; Epithelial Cells; Humans; Hyperthermia; Primary Cell Culture; Sweat Glands; Sweating
PubMed: 34997030
DOI: 10.1038/s41598-021-03991-5 -
BMC Veterinary Research Jan 2023Canine mammary tumors (CMTs) have a poor prognosis, along with tumor recurrence and metastasis. Cell lines are vital in vitro models for CMT research. Many CMT...
BACKGROUND
Canine mammary tumors (CMTs) have a poor prognosis, along with tumor recurrence and metastasis. Cell lines are vital in vitro models for CMT research. Many CMT epithelial cell lines were reported. However, canine mammary myoepithelial cells, the contractile component of the canine mammary tissue were overlooked. This study aimed at establishing such a cell line. CMT-1 cell line was obtained from a canine mammary tumor CMT-1 and characterized molecularly through qPCR, western blotting, immunochemistry and immunofluorescence. Its doubling time, cytogenetic analysis and migration rate were evaluated using growth study, karyotype analysis and wound healing assay respectively. To determine its tumorigenesis, xenograft transplantation was performed.
RESULTS
CMT-1 tumor was a complex canine mammary carcinoma that stained negative to estrogen receptors (ER) and progesterone receptors (PR), but positive to human epidermal growth receptor-2 (HER2), defined as HER2-enriched subtype. In this study, a CMT-1 cell line obtained from CMT-1 tumor was immune-positive to vimentin, α-SMA, p63 and negative to E-cadherin (E-cad), indicating CMT-1 cells were myoepithelial cells. It was successfully cultured for more than 50 passages showing the same immunoreactivity to ER, PR, and HER2 as the primary canine tumor. The doubling time of CMT-1 cell line was 26.67 h. The chromosome number of CMT-1 cells ranged from 31 to 64. A potential spontaneous epithelial to mesenchymal transition (EMT) was noticed during cell cultures. Potential EMT-induced CMT-1 cells showed no significance in migration rate compared to the original CMT-1 cells. CMT-1 cells was able to grow on a 3D culture and formed grape-like, solid, and cystic mammospheres at different time period. Inoculation of CMT-1 cells induced a complex HER2-enriched mammary tumor with metastasis in mice.
CONCLUSIONS
A canine cancerous HER2-enriched myoepithelial cell line was successfully established and a canine mammosphere developed from myoepithelial cells was documented in this study. We are expecting this novel cell line and its associated mammospheres could be used as a model to elucidate the role of myoepithelial cells in CMT carcinogensis in the future.
Topics: Animals; Dogs; Mice; Cell Line, Tumor; Dog Diseases; Epithelial-Mesenchymal Transition; Mammary Neoplasms, Animal; Neoplasm Recurrence, Local
PubMed: 36717813
DOI: 10.1186/s12917-023-03573-9 -
PloS One 2022Mammary gland is present in all mammals and usually functions in producing milk to feed the young offspring. Mammogenesis refers to the growth and development of mammary...
Mammary gland is present in all mammals and usually functions in producing milk to feed the young offspring. Mammogenesis refers to the growth and development of mammary gland, which begins at puberty and ends after lactation. Pregnancy is regulated by various cytokines, which further contributes to mammary gland development. Epithelial cells, including basal and luminal cells, are one of the major components of mammary gland cells. The development of basal and luminal cells has been observed to significantly differ at different stages. However, the underlying mechanisms for differences between basal and luminal cells have not been fully studied. To explore the mechanisms underlying the differentiation of mammary progenitors or their offspring into luminal and myoepithelial cells, the single-cell sequencing data on mammary epithelia cells of virgin and pregnant mouse was deeply investigated in this work. We evaluated features by using Monte Carlo feature selection and plotted the incremental feature selection curve with support vector machine or RIPPER to find the optimal gene features and rules that can divide epithelial cells into four clusters with different cell subtypes like basal and luminal cells and different phases like pregnancy and virginity. As representations, the feature genes Cldn7, Gjb6, Sparc, Cldn3, Cited1, Krt17, Spp1, Cldn4, Gjb2 and Cldn19 might play an important role in classifying the epithelial mammary cells. Notably, seven most important rules based on the combination of cell-specific and tissue-specific expressions of feature genes effectively classify the epithelial mammary cells in a quantitative and interpretable manner.
Topics: Animals; Cell Differentiation; Epithelial Cells; Female; Lactation; Mammals; Mammary Glands, Animal; Mice; Pregnancy; Sexual Maturation
PubMed: 35486595
DOI: 10.1371/journal.pone.0267211 -
Journal of Pharmacy & Bioallied Sciences Apr 2015Myoepithelial cells are a normal constituent of the salivary acini and ducts and are found between the epithelial cells and the basement membrane. Microscopically... (Review)
Review
Myoepithelial cells are a normal constituent of the salivary acini and ducts and are found between the epithelial cells and the basement membrane. Microscopically myoepithelial cells are thin and spindle-shaped and ultrastructurally they possess a number of Cytoplasmic processes that extend between and over the acinar and ductal-lining cells, and they show features of both smooth muscle and epithelium. They play a vital role during expulsion of saliva and regulates the electrolytic exchange. They also perform as tumor suppressors and are considered to play a very important role in differentiation of various salivary gland tumors and help in the diagnosis of tumors. Neoplastic myoepithelial cells in both benign and malignant tumors can take numerous forms including epithelioid, plasmacytoid, spindle and clear cell variant, and this variability largely accounts for difficulties in histopathological diagnosis.
PubMed: 26015706
DOI: 10.4103/0975-7406.155898 -
Diagnostic Pathology Feb 2021A 52-year-old woman presented with shortness of breath and cough. An endobronchial sialolipoma was found at the left entrance of the main bronchus. Sialolipoma is an...
BACKGROUND
A 52-year-old woman presented with shortness of breath and cough. An endobronchial sialolipoma was found at the left entrance of the main bronchus. Sialolipoma is an exceedingly rare type of lipoma reported of the minor salivary glands, especially within the bronchus.
CASE PRESENTATION
A 52-year-old woman presented with shortness of breath and cough with 6 months´ evolution. Endobronchial endoscopy revealed a tumour at the left entrance of the main bronchus. The entire removal of the tumour was removed using a cryoprobe device. Pathological examination showed a tumour consistent with the diagnosis of sialolipoma due to the presence of mature adipose cells blended with acinar, ductal, basal, and myoepithelial cells. The patient had a favourable outcome.
CONCLUSION
The infrequent tracheobronchial presentation of this tumour can be challenging for correct diagnosis.
Topics: Adipocytes; Diagnosis, Differential; Endoscopy; Female; Humans; Lipoma; Middle Aged; Salivary Glands, Minor; Submandibular Gland Neoplasms
PubMed: 33612094
DOI: 10.1186/s13000-021-01074-7