Dataset Information

Characterization of Primary Epithelial Cells Derived from Human Salivary Gland Contributing to in vivo Formation of Acini-like Structures.

ABSTRACT: Patients with head and neck cancer are treated with therapeutic irradiation, which can result in irreversible salivary gland dysfunction. Because there is no complete cure for such patients, stem cell therapy is an emerging alternative for functional restoration of salivary glands. In this study, we investigated in vitro characteristics of primarily isolated epithelial cells from human salivary gland (Epi-SGs) and in vivo formation of acini-like structures by Epi-SGs. Primarily isolated Epi-SGs showed typical epithelial cell-like morphology and expressed E-cadherin but not N-cadherin. Epi-SGs expressed epithelial stem cell (EpiSC) and embryonic stem cell (ESC) markers. During long-term culture, the expression of EpiSC and ESC markers was highly detected and maintained within the core population with small size and low cytoplasmic complexity. The core population expressed cytokeratin 7 and cytokeratin 14, known as duct markers indicating that Epi-SGs might be originated from the duct. When Epi-SGs were transplanted in vivo with Matrigel, acini-like structures were readily formed at 4 days after transplantation and they were maintained at 7 days after transplantation. Taken together, our data suggested that Epi-SGs might contain stem cells which were positive for EpiSC and ESC markers, and Epi-SGs might contribute to the regeneration of acini-like structures in vivo. We expect that Epi-SGs will be useful source for the functional restoration of damaged salivary gland.

SUBMITTER: Nam H

PROVIDER: S-EPMC6030237 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Characterization of Primary Epithelial Cells Derived from Human Salivary Gland Contributing to in vivo Formation of Acini-like Structures.

Nam Hyun H Kim Ji-Hye JH Hwang Ji-Yoon JY Kim Gee-Hye GH Kim Jae-Won JW Jang Mi M Lee Jong-Ho JH Park Kyungpyo K Lee Gene G

Molecules and cells 20180611 6

Patients with head and neck cancer are treated with therapeutic irradiation, which can result in irreversible salivary gland dysfunction. Because there is no complete cure for such patients, stem cell therapy is an emerging alternative for functional restoration of salivary glands. In this study, we investigated in vitro characteristics of primarily isolated epithelial cells from human salivary gland (Epi-SGs) and in vivo formation of acini-like structures by Epi-SGs. Primarily iso ...[more]

PMID: 29890826

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Project description:Primary Sjögren’s syndrome (SS or autoimmune epithelitis) is a relatively common autoimmune disorder that is primarily characterized by chronic lymphoepithelial inflammatory reactions in the exocrine glands, mainly the salivary and lachrymal glands. It may extend from disease confined to the exocrine glands (organ-specific exocrinopathy) to various extraglandular manifestations (systemic disease) and the development of B-cell lymphoma. Several studies from our laboratory had provided evidence for the strong implication of ductal salivary gland epithelial cells (SGEC) in the pathogenesis of Sjögren’s syndrome (SS), including the development of salivary gland infiltrating lesions and of adverse systemic clinical complications, such as the development of B-cell lymphoma. In fact, the comparative assessment of non-neoplastic SGEC lines derived from SS patients and disease controls had indicated that the ductal epithelia of SS patients manifest an “intrinsically activated” status that is associated with distinct aberrant phenotypic and functional features encountered in “inflamed” cells. Herein, using microarray analysis, we sought to comparatively analyze the constitutive gene expression in long-term cultured non-neoplastic SGEC lines derived from non-SS sicca control individuals and from SS patients. The study aimed to reveal the genes that are differentially expressed between SGEC lines derived from SS patients and controls, as well as between SGEC lines derived from SS patients with moderate lymphocytic infiltrations (focus score<2; SS-Group-1) and SS patients with severe lymphocytic infiltrations (focus score ≥2; SS-Group-2). The transcriptome profiling analysis presented herein lends further support to the intrinsic activation status of patients’ ductal epithelia and its association with distinct proinflammatory and metabolism-related gene signatures, which occur primarily among patients with heavy tissue infiltrates and high risk for lymphoma development.

Project description:BackgroundMyocardin-related transcription factors (MRTF) A and B link actin dynamics and mechanotransduction to gene expression. In mice, MRTF-A is involved in mammary gland differentiation, but its role in human mammary epithelial cells remains unclear.MethodsThree-dimensional cultures of human mammary epithelial MCF10A cells were used to model acinar morphogenesis. Stable MRTF-A knockdown, MRTF-A/B rescue and MRTF-A/B overexpression was established to characterize the functional role during morphogenesis using confocal microscopy and expression analysis. Breast cancer patient databases were analyzed for MRTF-A expression.ResultsWe showed that a precise temporal control of MRTFs is required for normal morphogenesis of MCF10A mammary acini. MRTF transcriptional activity, but not their protein amounts, is transiently induced during 3D acini formation. MRTF-A knockdown dramatically reduces acini size and prevents lumen formation. These effects are rescued by re-expression of MRTF-A, and partially by MRTF-B. Conversely, overexpression of MRTF-A and MRTF-B increases acini size, resulting in irregular spheroids without lumen and defective apico-basal polarity. These phenotypes correlate with deregulated expression of cell cycle inhibitors p21/Waf1, p27/Kip1 and altered phosphorylation of retinoblastoma protein. In MRTF overexpressing spheroids, proliferation and apoptosis are simultaneously increased at late stages, whilst neither occurs in control acini. MRTFs interfere with anoikis of the inner cells and cause an integrin switch from ?6 to ?5, repression of E-cadherin and induction of mesenchymal markers vimentin, Snai2 and Zeb1. Moreover, MRTF-overexpressing spheroids are insensitive to alteration in matrix stiffness. In two breast cancer cohorts, high expression of MRTF-A and known target genes was associated with decreased patient survival.ConclusionMRTF-A is required for proliferation and formation of mammary acini from luminal epithelial cells. Conversely, elevated MRTF activity results in pre-malignant spheroid formation due to defective proliferation, polarity loss and epithelial-mesenchymal transition.

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Characterization of Primary Epithelial Cells Derived from Human Salivary Gland Contributing to in vivo Formation of Acini-like Structures.

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Characterization of Primary Epithelial Cells Derived from Human Salivary Gland Contributing to <i>in vivo</i> Formation of Acini-like Structures.

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