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Nature Reviews. Cancer Oct 2017Metaplasia is the replacement of one differentiated somatic cell type with another differentiated somatic cell type in the same tissue. Typically, metaplasia is... (Review)
Review
Metaplasia is the replacement of one differentiated somatic cell type with another differentiated somatic cell type in the same tissue. Typically, metaplasia is triggered by environmental stimuli, which may act in concert with the deleterious effects of microorganisms and inflammation. The cell of origin for intestinal metaplasia in the oesophagus and stomach and for pancreatic acinar-ductal metaplasia has been posited through genetic mouse models and lineage tracing but has not been identified in other types of metaplasia, such as squamous metaplasia. A hallmark of metaplasia is a change in cellular identity, and this process can be regulated by transcription factors that initiate and/or maintain cellular identity, perhaps in concert with epigenetic reprogramming. Universally, metaplasia is a precursor to low-grade dysplasia, which can culminate in high-grade dysplasia and carcinoma. Improved clinical screening for and surveillance of metaplasia might lead to better prevention or early detection of dysplasia and cancer.
Topics: Adaptation, Biological; Animals; Barrett Esophagus; Epigenesis, Genetic; Epithelium; Gastric Mucosa; Humans; Intestinal Mucosa; Metaplasia; Mucous Membrane; Respiratory Mucosa; Transcription Factors
PubMed: 28860646
DOI: 10.1038/nrc.2017.68 -
The Journal of Physiology Sep 2018The development of intestinal-type gastric cancer is preceded by the emergence of metaplastic cell lineages in the gastric mucosa. In particular, intestinal metaplasia... (Review)
Review
The development of intestinal-type gastric cancer is preceded by the emergence of metaplastic cell lineages in the gastric mucosa. In particular, intestinal metaplasia and spasmolytic polypeptide-expressing metaplasia (SPEM) have been associated with the pathological progression to intestinal-type gastric cancer. The development of SPEM represents a physiological response to damage that recruits reparative cells to sites of mucosal injury. Metaplastic cell lineages are characterized by mucus secretion, adding a protective barrier to the epithelium. Increasing evidence indicates that the influence of alarmins and cytokines is required to initiate the process of metaplasia development. In particular, IL-33 derived from epithelial cells stimulates IL-13 production by specialized innate immune cells to induce chief cell transdifferentiation into SPEM following the loss of parietal cells from the corpus of the stomach. While SPEM represents a physiological healing response to acute injury, persistent injury and chronic inflammation can perpetuate a recurring pattern of reprogramming and metaplasia that is a risk factor for gastric cancer development. The transdifferentiation of zymogen secreting cells into mucous cell metaplasia may represent both a general repair mechanism in response to mucosal injury in many epithelia as well as a common pre-neoplastic pathway associated with chronic injury and inflammation.
Topics: Animals; Humans; Inflammation; Intercellular Signaling Peptides and Proteins; Interleukin-13; Intestines; Metaplasia; Parietal Cells, Gastric; Stomach
PubMed: 29427515
DOI: 10.1113/JP275512 -
Biochimica Et Biophysica Acta. Reviews... Mar 2022Pancreatic ductal metaplasia (PDM) is the transformation of potentially many type of cells in pancreas into ductal or ductal-like cells, which eventually replace the... (Review)
Review
Pancreatic ductal metaplasia (PDM) is the transformation of potentially many type of cells in pancreas into ductal or ductal-like cells, which eventually replace the existing differentiated somatic cell type(s). PDM is usually triggered by and manifests its ability to adapt to environmental and cellular stimuli and stresses. Acinar to ductal metaplasia (ADM) is the predominant form of ductal metaplasia in pancreas. The cellular heterogeneity of PDM informs the differences in cellular origin, triggering events, functional subpopulations and evolution pathways of PDM. Currently it remains uncertain what are the exact cellular origins and functional significance of PDM, and how this process is regulated at cellular and molecular levels. The development of PDM to atypical hyperplasia is an important risk factor for pancreatic precursors, including intraepithelial neoplasia (PanIN), and pancreatic ductal adenocarcinoma (PDAC). Otherwise, the cellular plasticity in PDM contribute to the regeneration of both exocrine and endocrine components of pancreas. This Review will systematically describe current knowledge on the understanding of PDM biology with an emphasis on its underlying mechanisms and implications in pancreatic regeneration, inflammation and tumorigenesis.
Topics: Acinar Cells; Carcinoma, Pancreatic Ductal; Humans; Metaplasia; Pancreas; Pancreatic Neoplasms
PubMed: 35176433
DOI: 10.1016/j.bbcan.2022.188698 -
Gastroenterology Feb 2020
Topics: Biopsy; Endoscopy, Gastrointestinal; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Humans; Metaplasia; Population Surveillance; Precancerous Conditions; Risk Factors; Stomach Neoplasms
PubMed: 31816298
DOI: 10.1053/j.gastro.2019.12.003 -
Gastroenterology Jan 2021In stomach, metaplasia can arise from differentiated chief cells that become mitotic via paligenosis, a stepwise program. In paligenosis, mitosis initiation requires...
BACKGROUND AND AIMS
In stomach, metaplasia can arise from differentiated chief cells that become mitotic via paligenosis, a stepwise program. In paligenosis, mitosis initiation requires reactivation of the cellular energy hub mTORC1 after initial mTORC1 suppression by DNA damage induced transcript 4 (DDIT4 aka REDD1). Here, we use DDIT4-deficient mice and human cells to study how metaplasia increases tumorigenesis risk.
METHODS
A tissue microarray of human gastric tissue specimens was analyzed by immunohistochemistry for DDIT4. C57BL/6 mice were administered combinations of intraperitoneal injections of high-dose tamoxifen (TAM) to induce spasmolytic polypeptide-expressing metaplasia (SPEM) and rapamycin to block mTORC1 activity, and N-methyl-N-nitrosourea (MNU) in drinking water to induce spontaneous gastric tumors. Stomachs were analyzed for proliferation, DNA damage, and tumor formation. CRISPR/Cas9-generated DDIT4 and control human gastric cells were analyzed for growth in vitro and in xenografts with and without 5-fluorouracil (5-FU) treatment.
RESULTS
DDIT4 was expressed in normal gastric chief cells in mice and humans and decreased as chief cells became metaplastic. Paligenotic Ddit4 chief cells maintained constitutively high mTORC1, causing increased mitosis of metaplastic cells despite DNA damage. Lower DDIT4 expression correlated with longer survival of patients with gastric cancer. 5-FU-treated DDIT4 human gastric epithelial cells had significantly increased cells entering mitosis despite DNA damage and increased proliferation in vitro and in xenografts. MNU-treated Ddit4 mice had increased spontaneous tumorigenesis after multiple rounds of paligenosis induced by TAM.
CONCLUSIONS
During injury-induced metaplastic proliferation, failure of licensing mTORC1 reactivation correlates with increased proliferation of cells harboring DNA damage, as well as increased tumor formation and growth in mice and humans.
Topics: Animals; Carcinogenesis; Cell Culture Techniques; Cell Proliferation; Chief Cells, Gastric; Humans; Metaplasia; Mice; Mice, Inbred C57BL; Transcription Factors
PubMed: 32956680
DOI: 10.1053/j.gastro.2020.09.016 -
BMJ Case Reports Aug 2018Keratinising squamous metaplasia of the bladder is a very rare entity that carries a risk of progression to malignancy. We present a case of a 62-year-old man found to... (Review)
Review
Keratinising squamous metaplasia of the bladder is a very rare entity that carries a risk of progression to malignancy. We present a case of a 62-year-old man found to have the condition and discuss the management dilemma with a review of the literature.
Topics: Biopsy; Cystoscopy; Disease Progression; Humans; Keratins; Male; Metaplasia; Middle Aged; Precancerous Conditions; Tomography, X-Ray Computed; Urinary Bladder
PubMed: 30115715
DOI: 10.1136/bcr-2018-225303 -
Differentiation; Research in Biological... Jul 2005There is currently much interest in the possibility to treat chronic diseases by cell replacement or regenerative therapies. Most of these studies focus on the... (Review)
Review
There is currently much interest in the possibility to treat chronic diseases by cell replacement or regenerative therapies. Most of these studies focus on the manipulation of undifferentiated stem cells. However, tissue repair and regeneration can also be achieved by differentiated cells, which, in certain conditions, can even transdifferentiate to other cell types. Such transdifferentiations can lead to tissue metaplasia. The pancreas is an organ wherein metaplasia has been well investigated and for which experimental models have been recently developed allowing to unravel the molecular basis of transdifferentiation. Pancreatic metaplasias studied so far include the conversion of exocrine acinar cells to duct cells, exocrine cells to endocrine islet cells, endocrine cells to duct cells, and acinar cells to hepatocytes. Epitheliomesenchymal transitions have also been described. The available evidence indicates that mature cells can be reprogrammed by specific environmental cues inducing the expression of cell type-specific transcription factors. For example, the glucocorticoid hormone dexamethasone induces pancreatic transdifferentiation to hepatocytes, whereas the combination of epidermal growth factor and leukemia-inhibitory factor induces exocrine-endocrine transdifferentiation in vitro. Further unravelling of the involved signal transduction pathways, transcription factor networks, and chromatin modifications is required to manipulate metaplasia at will and to apply it in tissue repair or regeneration.
Topics: Animals; Cell Differentiation; Humans; Metaplasia; Pancreas; Pancreatic Diseases
PubMed: 16138828
DOI: 10.1111/j.1432-0436.2005.00030.x -
Pathology, Research and Practice Jun 2020Main study: undertake a histological study of odontogenic cysts (OC) to determine the prevalence of dystrophic calcification and metaplasia to respiratory epithelium on... (Review)
Review
Dystrophic calcification and respiratory metaplasia in the epithelial lining of odontogenic cysts: a study of 362 odontogenic cysts in a Brazilian population and literature review.
PURPOSE
Main study: undertake a histological study of odontogenic cysts (OC) to determine the prevalence of dystrophic calcification and metaplasia to respiratory epithelium on a Brazilian population.
LITERATURE REVIEW
to review the literature for studies that investigated the prevalence of respiratory metaplasia and dystrophic calcification on OC.
METHODS
Main study: a retrospective histopathological evaluation was made of the archives from a pathology laboratory. A total of 362 cases diagnosed as OC were identified; they were analyzed by two expert observers to determine the presence of dystrophic calcification and respiratory metaplasia. The association with sex, age and anatomic location was performed through statistical analysis.
LITERATURE REVIEW
a critical literature review was undertaken. Two main electronic databases (PubMed and LILACS) were searched. Retrospective studies of histological evaluation that determined the prevalence of epithelial metaplasia and dystrophic calcification on OC, with at least 10 cases, were included; their findings were summarized and discussed.
RESULTS
Main study: the histological evaluation of OC revealed the presence of respiratory epithelium in 25 cases (6.9%) and dystrophic calcification in 24 cases (6.6%). Positive association was found to dystrophic calcification on residual cyst and age; respiratory metaplasia on OC and sex; respiratory metaplasia on residual cyst and gnatic bone; respiratory metaplasia in OC and gnatic bone; dystrophic calcification in OC and anatomic site of mandible.
LITERATURE REVIEW
eleven studies were included in the literature review, and respiratory metaplasia ranged from 0.0% to 19.2% while dystrophic calcification ranged from 2.5% to 40.5%.
CONCLUSIONS
the histological evaluation of this study found 6.9% of prevalence of respiratory metaplasia and 6.6% of dystrophic calcification, which is in accordance with the literature reviewed. Therefore, these phenomena must be taken into account in routine diagnosis services.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Brazil; Calcinosis; Child; Child, Preschool; Female; Humans; Jaw Diseases; Male; Metaplasia; Middle Aged; Odontogenic Cysts; Prevalence; Respiratory Mucosa; Retrospective Studies; Young Adult
PubMed: 32360248
DOI: 10.1016/j.prp.2020.152975 -
Gastroenterology Feb 2020
Topics: Algorithms; Biopsy; Endoscopy, Gastrointestinal; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Humans; Metaplasia; Population Surveillance; Practice Guidelines as Topic; Precancerous Conditions; Risk Factors; Stomach Neoplasms
PubMed: 32035529
DOI: 10.1053/j.gastro.2020.01.012 -
Diagnostic Cytopathology May 2019Hürthle cell (HC) metaplasia is an important feature of chronic lymphocytic (Hashimoto) thyroiditis (HT). However, it is rarely observed in juvenile form HT. In a study... (Review)
Review
OBJECTIVES
Hürthle cell (HC) metaplasia is an important feature of chronic lymphocytic (Hashimoto) thyroiditis (HT). However, it is rarely observed in juvenile form HT. In a study based on fine needle aspiration cytology, the cytomorphological difference between pediatric HT and its adult form was studied, with special attention on HC metaplasia and its pathogenesis.
MATERIALS AND METHODS
The frequency of following 12 cytomorphological features in 16 pediatric and 104 adult HT cases were compared: follicular cells, lymphoid cells, HCs, plasma cells, lympho-histiocytic aggregates, epithelioid histiocytes, multinucleated giant cells, fire-flare appearance, colloid, intracytoplasmic lumen (ICL) with or without colloid inclusion, paravacuolar granules, and cyst cells. The age decade distribution of HC metaplasia was analyzed.
RESULTS
Significant difference was observed between pediatric HT and its adult form in respect of HC metaplasia and ICL with colloid inclusion in HC. HC were present in 7 (43.8%) of pediatric and 94 (90.4%) of adult HT cases (P = 0.00006). 1 (6.3%) pediatric and 35 (33.7%) adult HT cases had ICL with colloid inclusion in HC (P = 0.03698). As compared to first two decades of life, significantly higher number of cases revealed HC metaplasia in every decade from third decade onwards (P = 0.01290-0.00009); however, the difference in respect of ICL with colloid inclusions attained significance during sixth decade only (P = 0.00235).
CONCLUSIONS
Hürthlization, which appears to be survival response, is rare in pediatric HT and becomes more pronounced starting from third decade onwards; significant increase in ICL with colloid inclusion is a much more delayed phenomenon.
Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Child; Female; Hashimoto Disease; Humans; Male; Metaplasia; Middle Aged; Oxyphil Cells
PubMed: 30588770
DOI: 10.1002/dc.24140