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Head and Neck Pathology Jul 2013Epithelial myoepithelial carcinoma (EMCa) is a rare but well characterized biphasic salivary gland malignancy with several variant morphologies. Oncocytic and apocrine... (Review)
Review
Epithelial myoepithelial carcinoma (EMCa) is a rare but well characterized biphasic salivary gland malignancy with several variant morphologies. Oncocytic and apocrine EMCa are uncommon variants that constitute up to 8 % of all EMCa. Both variants invoke an eosinophilic or oncocytic differential diagnosis and challenge the traditional requirement of clear myoepithelial cells for EMCa. Oncocytic EMCa occurs in patients a decade older than conventional EMCa. This variant is often papillary with calcification and associated with sebaceous components and occurs in older individuals. Apocrine EMCa is named for its apocrine ductal component, which may be mistaken for salivary duct carcinoma. In this variant, the epithelial component often shows overgrowth in a cribriform or even solid pattern and is immunophenotypically defined by androgen receptor and gross cystic disease fluid protein 15 positivity. The most important aspect of differentiating both oncocytic and apocrine EMCa from other salivary oncocytic tumors is recognition of the biphasic nature of these variants and confirmation that the abluminal outer layer consists of plump, 'activated' myoepithelial cells, regardless of tinctorial characteristics. Both oncocytic and apocrine EMCa behave very indolently in the limited literature to date.
Topics: Apocrine Glands; Biomarkers, Tumor; Carcinoma; Humans; Myoepithelioma; Oxyphil Cells; Salivary Gland Neoplasms
PubMed: 23821213
DOI: 10.1007/s12105-013-0461-0 -
Head and Neck Pathology Sep 2012Middle ear adenomas (MEAs) are benign neoplasms along a spectrum with neuroendocrine neoplasms (carcinoid tumors). Immunohistochemical (IHC) staining for myoepithelial...
Middle ear adenomas (MEAs) are benign neoplasms along a spectrum with neuroendocrine neoplasms (carcinoid tumors). Immunohistochemical (IHC) staining for myoepithelial markers has not been reported in these tumors. The archives of the Cleveland Clinic, University of Virginia and Armed Forces Institute of Pathology were retrospectively searched for tumors arising within the middle ear with material available for IHC staining. Twelve cases of MEAs, four cases of jugulotympanic paragangliomas (JPGs), 10 cases of ceruminous adenomas (CAs) and four cases of ceruminous adenocarcinomas (CACs) were obtained. IHC staining was performed for smooth muscle actin (SMA), p63, S-100 protein, cytokeratin 5/6 (CK5/6), and cytokeratin 7 (CK7). The MEAs were positive for: CK7 (92 %, luminal), CK5/6 (92 %, abluminal), p63 (83 %, abluminal), and negative for SMA and S-100 protein. The JPGs were negative for CK7, CK5/6, p63 and SMA; S-100 protein highlighted sustentacular cells. The CAs were positive for: CK7 (100 %, luminal), CK5/6 (100 %, abluminal), S-100 protein (80 %, abluminal), p63 (100 %, abluminal), and SMA (90 %, abluminal). CACs demonstrated two patterns, (1) adenoid cystic carcinoma-type: positive for CK7 (100 %, luminal), CK5/6, S-100 protein, p63, and SMA (all 100 %, abluminal); and (2) conventional-type: CK7 (50 % luminal), and no CK5/6, SMA, S-100 protein, or p63 expression. The IHC profile of MEAs suggests that these tumors harbor at least two cell populations, including luminal and basal cells. However, unlike ceruminous adenomas, MEAs lack true myoepithelial differentiation given the absence of S-100 protein and SMA staining in all cases.
Topics: Adenocarcinoma; Adenoma; Adolescent; Adult; Aged; Cell Differentiation; Diagnosis, Differential; Ear Neoplasms; Ear, Middle; Epithelial Cells; Female; Humans; Immunohistochemistry; Male; Middle Aged; Muscle, Smooth; Paraganglioma; Retrospective Studies; Young Adult
PubMed: 22623086
DOI: 10.1007/s12105-012-0365-4 -
International Journal of Experimental... Aug 1998The rodent and human nonpregnant mammary glands contain epithelial, intermediate and myoepithelial cells which have all been isolated as cell lines in vitro.... (Review)
Review
The rodent and human nonpregnant mammary glands contain epithelial, intermediate and myoepithelial cells which have all been isolated as cell lines in vitro. Transforming growth factor-alpha (TGF alpha) and basic fibroblast growth factor (bFGF) are produced by myoepithelial cells and can stimulate the growth of intermediate stem cells in vitro. Epithelial and intermediate cells behave like stem cells in vitro, since they can differentiate into alveolar-like an myoepithelial cells. The myoepithelial differentiation pathway is associated with the early expression of a calcium-binding regulatory protein called p9Ka and the protease, Cathepsin D. Myoepithelial cells are also present in benign lesions but not in malignant mammary carcinomas of rats or humans, whose resultant cell lines fail to differentiate completely along the myoepithelial cell pathway. Loss of the myoepithelial cell in some invasive carcinomas may be compensated, at least in part, by changes in malignant cells. Over-expression of TGF alpha and/or erbB receptors may reduce the requirement for TGF alpha, whilst ectopic production of bFGF and its receptors and p9Ka/Cathespin D may assist in tumorigenesis and in metastasis, respectively. Thus compensation for, or retention of, molecules potentially involved in the differentiation of mammary cells may be a mechanism by which malignancy progresses in some human invasive carcinomas.
Topics: Animals; Antigens, Differentiation; Breast; Breast Neoplasms; Cell Differentiation; Cell Transformation, Neoplastic; Epithelium; Female; Growth Substances; Hormones; Humans; Mammary Glands, Animal; Micronutrients; Pituitary Gland; Rats; Stem Cells
PubMed: 9797716
DOI: 10.1046/j.1365-2613.1998.00068.x -
Cold Spring Harbor Perspectives in... Nov 2010The mammary gland is composed of a diverse array of cell types that form intricate interaction networks essential for its normal development and physiologic function.... (Review)
Review
The mammary gland is composed of a diverse array of cell types that form intricate interaction networks essential for its normal development and physiologic function. Abnormalities in these interactions play an important role throughout different stages of tumorigenesis. Branching ducts and alveoli are lined by an inner layer of secretory luminal epithelial cells that produce milk during lactation and are surrounded by contractile myoepithelial cells and basement membrane. The surrounding stroma comprised of extracellular matrix and various cell types including fibroblasts, endothelial cells, and infiltrating leukocytes not only provides a scaffold for the organ, but also regulates mammary epithelial cell function via paracrine, physical, and hormonal interactions. With rare exceptions breast tumors initiate in the epithelial compartment and in their initial phases are confined to the ducts but this barrier brakes down with invasive progression because of a combination of signals emitted by tumor epithelial and various stromal cells. In this article, we overview the importance of cellular interactions and microenvironmental signals in mammary gland development and cancer.
Topics: Animals; Breast; Breast Neoplasms; Cell Differentiation; Disease Models, Animal; Epithelial Cells; Extracellular Matrix; Female; Humans; Mammary Glands, Animal; Mammary Neoplasms, Experimental; Tumor Microenvironment
PubMed: 20591988
DOI: 10.1101/cshperspect.a003244 -
Experimental Cell Research Jul 2022Myoepithelial cells (MECs) are responsible for receiving stimuli from the central nervous system and translating their responses into the form of secretion into...
Myoepithelial cells (MECs) are responsible for receiving stimuli from the central nervous system and translating their responses into the form of secretion into glandular tissue, including salivary glands (SG), sweet glands, and mammary glands. SG MECs cause the secretion of serous saliva by contracting of acini/ductal cells with acetylcholine (Ach) from parasympathetic nerves via muscarinic receptors. To response the parasympathetic physiological stimulation, SG epithelial cell-derived MECs are supposed to be induced and placed adjacent to parasympathetic system nerve ends in SGs by forming a neuro-myoepithelial junction. For salivary secretion to function under parasympathetic control, therefore, specific regions of salivary gland epithelial cells must be mapped and the epithelium near the nerve must differentiate into MECs in order to form a nerve-myoepithelial junction during organogenesis. We hypothesized that the epithelium near the parasympathetic nerves is induced the differentiation into MECs by which the neurotransmitter acetylcholine via muscarinic receptors. qPCR and whole-mount immunohistochemical analysis in ex vivo organ culture system revealed that SG epithelial cells near a parasympathetic nerve were found to be induced to differentiate into MECs via the cholinergic receptor muscarinic 1 by carbachol (CCh), an acetylcholine agonist. In addition, CCh stimulated ERK and Akt signaling for the induction of MEC differentiation in rat submandibular gland epithelial cells. These findings indicate that muscarinic action is required for the induction of MECs and formation of a neuro-myoepithelial junction in developing SGs. This study proposes a novel concept for tissue architecture to form a neuro-myoepithelial junction during neurofunctional organogenesis including SGs.
Topics: Acetylcholine; Animals; Cell Differentiation; Cholinergic Agents; Epithelial Cells; Neurotransmitter Agents; Organogenesis; Rats; Receptors, Muscarinic; Salivary Glands; Submandibular Gland
PubMed: 35427599
DOI: 10.1016/j.yexcr.2022.113137 -
Stem Cell Research & Therapy Nov 2021Diabetes mellitus causes deterioration in the body, including serious damage of the oral cavity related to salivary gland dysfunction, characterised by hyposalivation...
OBJECTIVE
Diabetes mellitus causes deterioration in the body, including serious damage of the oral cavity related to salivary gland dysfunction, characterised by hyposalivation and xerostomia. Human dental pulp stem cells (hDPSCs) represent a promising therapy source, due to the easy, minimally invasive surgical access to these cells and their high proliferative capacity. It was previously reported that the trophic support mediated by these cells can rescue the functional and structural alterations of damaged salivary glands. However, potential differentiation and paracrine effects of hDPSCs in diabetic-induced parotid gland damage have not been investigated. Our study aimed to investigate the therapeutic effects of intravenous transplantation of hDPSCs on parotid gland injury in a rat model of streptozotocin (STZ)-induced type 1 diabetes.
METHODS
Thirty Sprague-Dawley male rats were randomly categorised into three groups: control, diabetic (STZ), and transplanted (STZ + hDPSCs). The hDPSCs or the vehicles were injected into the rats' tail veins, 7 days after STZ injection. Fasting blood glucose levels were monitored weekly. A glucose tolerance test was performed, and the parotid gland weight, salivary flow rate, oxidative stress indices, parotid gland histology, and caspase-3, vascular endothelial growth factor, proliferating cell nuclear antigen, neuronal nitric oxide synthase, endothelial nitric oxide synthase, and tetrahydrobiopterin biosynthetic enzyme expression levels in parotid tissues were assessed 28 days post-transplantation.
RESULTS
Transplantation of hDPSCs decreased blood glucose, improved parotid gland weight and salivary flow rate, and reduced oxidative stress. The cells migrated to the STZ-injured parotid gland and differentiated into acinar, ductal, and myoepithelial cells. Moreover, hDPSCs downregulated the expression of caspase-3 and upregulated the expression of vascular endothelial growth factor and proliferating cell nuclear antigen, likely exerting pro-angiogenic and anti-apoptotic effects and promoting endogenous regeneration. In addition, the transplanted cells enhanced the parotid nitric oxide-tetrahydrobiopterin pathway.
CONCLUSIONS
Our results showed that hDPSCs migrated to and survived within the STZ-injured parotid gland, where functional and morphological damage was prevented due to the restoration of normal glucose levels, differentiation into parotid cell populations, and stimulation of paracrine-mediated regeneration. Thus, hDPSCs may have potential in the treatment of diabetes-induced parotid gland injury.
Topics: Animals; Dental Pulp; Humans; Male; Parotid Gland; Rats; Rats, Sprague-Dawley; Stem Cells; Streptozocin; Vascular Endothelial Growth Factor A
PubMed: 34775989
DOI: 10.1186/s13287-021-02646-6 -
Cell Proliferation Oct 2003Breast epithelial stem cells are thought to be the primary targets in the aetiology of breast cancer. As breast cancers are predominantly oestrogen and progesterone... (Review)
Review
Breast epithelial stem cells are thought to be the primary targets in the aetiology of breast cancer. As breast cancers are predominantly oestrogen and progesterone receptor-positive (ERalpha/PR+), we investigated the biology of ERalpha/PR+ cells and their relationship to stem cells in normal human breast epithelium. Several complementary approaches were used to characterize the stem-cell population and relate it to ERalpha/PR+ cells, including dual label colocalization on tissue sections, isolation of a Hoechst dye-effluxing 'side population' using flow cytometry, and examination of DNA label retention. The intermediate or suprabasal population suggested by others to be breast stem cells comprises ERalpha/PR+ cells that coexpress the putative stem-cell markers including cytokeratin 19. Human breast epithelial cells with Hoechst dye-effluxing 'side population' properties characteristic of mammary stem cells in mice were demonstrated by lack of expression of myoepithelial and luminal cell-specific antigens such as CALLA and MUC1 to be undifferentiated cells. Using DNA radiolabelling of human tissue implanted into athymic nude mice, a population of label-retaining putative stem cells (LRC) were shown to be enriched for cells expressing the putative stem-cell markers p21CIP1/WAF1 and Musashi-1, which, interestingly, were expressed in separate subpopulations of ERalpha/PR+ cells. Finally, expression patterns of Musashi-1 and Notch-1 in relation to ERalpha/PR+ and adjacent proliferating cells suggest that the evolutionarily conserved Delta/Notch signalling pathway regulates asymmetric division of the putative stem-cell population. The data suggest a model in which ERalpha/PR+ cells scattered through the epithelium are stem cells that self-renew through asymmetric cell division and generate patches of transit amplifying and differentiated cells. ERalpha/PR+ breast cancers exhibit loss of the two key regulators of asymmetric cell division, Musashi-1 and Notch-1 and thus may arise from symmetric division of the ERalpha/PR+ stem cell.
Topics: Breast; Epithelial Cells; Humans; Stem Cells
PubMed: 14521515
DOI: 10.1046/j.1365-2184.36.s.1.5.x -
Cell Proliferation Oct 2003The majority of human breast carcinomas exhibit luminal characteristics and as such, are most probably derived from progenitor cells within the luminal epithelial... (Review)
Review
The majority of human breast carcinomas exhibit luminal characteristics and as such, are most probably derived from progenitor cells within the luminal epithelial compartment. This has been subdivided recently into at least three luminal subtypes based on gene expression patterns. The value of knowing the cellular origin of individual tumours is clear and should aid in designing effective therapies. To do this, however, we need strategies aimed at defining the nature of stem and progenitor cell populations in the normal breast. In this review, we will discuss our technical approach for delineating the origin of the epithelial cell types. A major step forward was the purification of each cell type by the application of immunomagnetic cell sorting based on expression of lineage-specific surface antigens. We then developed chemically defined media that could support either the luminal epithelial or the myoepithelial cell phenotype in primary cultures. Having succeeded in continuous propagation presumably without loss of markers, we could show that a subset of the luminal epithelial cells could convert to myoepithelial cells, signifying the possible existence of a progenitor cell population. By combining the information on marker expression and in situ localization with immunomagnetic sorting and subsequent immortalization, we have identified and isolated a cytokeratin 19-positive suprabasal putative precursor cell in the luminal epithelial compartment and established representative cell lines. This suprabasal-derived epithelial cell line is able to generate both itself and differentiated luminal epithelial and myoepithelial cells, and in addition, is able to form elaborate terminal duct lobular unit (TDLU)-like structures within a reconstituted basement membrane. As more than 90% of breast cancers arise in TDLUs and more than 90% are also cytokeratin 19-positive, we suggest that this cell population contains a breast-cancer progenitor.
Topics: Breast; Breast Neoplasms; Cell Line; Epithelial Cells; Humans; Stem Cells
PubMed: 14521514
DOI: 10.1046/j.1365-2184.36.s.1.4.x -
Archives of Pathology & Laboratory... Apr 2011Numerous immunohistochemical stains have been shown to exhibit exclusive or preferential positivity in breast myoepithelial cells relative to their luminal/epithelial... (Review)
Review
CONTEXT
Numerous immunohistochemical stains have been shown to exhibit exclusive or preferential positivity in breast myoepithelial cells relative to their luminal/epithelial counterparts. These myoepithelial markers provide invaluable assistance in accurately classifying breast proliferations, especially in core biopsies. Although numerous myoepithelial markers are available, they differ in their sensitivity, specificity, and ease of interpretation, which may be attributed, to a large extent, to the variable immunoreactivity of these markers in stromal cells including myofibroblasts, vessels, luminal/epithelial cells, and tumor cells.
OBJECTIVE
To review commonly used myoepithelial markers in breast pathology and a selection of diagnostic scenarios where they may be useful.
DATA SOURCES
The information outlined in this review article is based on our experiences with routine cases and a review of English-language articles published between 1987 and 2008.
CONCLUSIONS
To demonstrate the presence or absence of myoepithelial cells, a panel-based approach of 2 or more markers is recommended. Markers that most effectively combine sensitivity, specificity, and ease of interpretation include smooth muscle myosin heavy chains, calponin, p75, p63, P-cadherin, basal cytokeratins, maspin, and CD10. These markers, however, display varying cross-reactivity patterns and variably reduced expression in the myoepithelial cells bordering in situ carcinomas. The choice of a myoepithelial marker should be dependent on a combination of factors, including published evidence on its diagnostic utility, its availability, performance characteristics that have been achieved in a given laboratory, and the specific diagnostic scenario. When its use is deemed necessary, immunohistochemistry for myoepithelial cells in breast pathology is most effective when conceptualized as supplemental, rather than central to routine morphologic interpretation.
Topics: Biomarkers, Tumor; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Epithelial Cells; Female; Humans; Immunohistochemistry; Myocytes, Smooth Muscle; Predictive Value of Tests
PubMed: 21466356
DOI: 10.5858/2010-0336-CP.1 -
Seminars in Cell & Developmental Biology Nov 2017Many tissues in our body have a tubular shape and are constantly exposed to various stresses. Luminal pressure imposes tension on the epithelial and myoepithelial or... (Review)
Review
Many tissues in our body have a tubular shape and are constantly exposed to various stresses. Luminal pressure imposes tension on the epithelial and myoepithelial or smooth muscle cells surrounding the lumen of the tubes. Contractile forces generated by actomyosin assemblies within these cells oppose the luminal pressure and must be calibrated to maintain tube diameter homeostasis and tissue integrity. In this review, we discuss mechanotransduction pathways that can lead from sensation of cell stretch to activation of actomyosin contractility, providing rapid mechanochemical feedback for proper tubular tissue function.
Topics: Actomyosin; Animals; Biomechanical Phenomena; Epithelial Cells; Homeostasis; Humans; Integrins; Signal Transduction
PubMed: 28610943
DOI: 10.1016/j.semcdb.2017.05.014