Expression of Embryonic Stem Cell Markers in Microcystic Lymphatic Malformation

Eady, Elizabeth K.; Brasch, Helen D.; Jongh, Jennifer de; Marsh, Reginald; Tan, Swee T.; Itinteang, Tinte

doi:10.1089/lrb.2018.0046

Cited by 9 publications

(8 citation statements)

References 33 publications

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“…The demonstration of cells in AVM that express stemness-associated markers may suggest the presence of ESC-like cells, and this warrants further investigation. The presence of such a primitive population would be consistent with the finding of ESC-like cells in other vascular anomalies such as infantile hemangioma (28), pyogenic granuloma (29), venous malformation (22), verrucous venous malformation (30), and lymphatic malformation (31).…”

Section: Discussionsupporting

confidence: 84%

“…iPSCs are generated from somatic cells by overexpression of transcription factors OCT4, SOX2, NANOG, KLF4, and c-MYC, which are markers of iPSCs and facilitate the reprogramming of somatic cells back to a pluripotent state (37). The presence of the stemness-associated markers within lymphatic malformation (31) and AVM suggests the presence of an iPSC phenomenon which may be initiated and perpetuated by certain somatic mutations. A causative link between the genetic instability of iPSCs during reprogramming and an increased risk of disease has been proposed (37), with pre-existing mutations in somatic cells identified as the primary cause (15).…”

Section: Discussionmentioning

confidence: 99%

“…We have previously demonstrated the presence of an ESClike population in vascular tumors (28,29) and vascular malformations (22,30,31). This study investigated the presence and expression pattern of OCT4, SOX2, NANOG, KLF4, and c-MYC in extracranial AVM, using immunohistochemical and immunofluorescence staining, in situ hybridization (ISH), reverse transcription quantitative polymerase chain reaction (RT-qPCR), and western blotting (WB).…”

Section: Introductionmentioning

confidence: 99%

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Stemness-Associated Markers Are Expressed in Extracranial Arteriovenous Malformation

et al. 2021

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Objectives: Arteriovenous malformation (AVM) consists of a nidus with poorly formed low-resistance vessels in place of a functional capillary network. The role of somatic mutations in embryonic stem cells (ESCs) and vascular anomalies and the presence of primitive populations in vascular anomalies led us to investigate the presence of a primitive population in extracranial AVM.Methods: Extracranial AVM tissue samples from 12 patients were stained for stemness-associated markers OCT4, SOX2, NANOG, KLF4, and c-MYC using immunohistochemical staining. In situ hybridization (ISH) was performed on six tissue samples to determine transcript expression. Western blotting and RT-qPCR were performed on two AVM-derived primary cell lines to determine protein and transcript expression of these markers, respectively. Immunofluorescence staining was performed on two tissue samples to investigate marker co-localization.Results: Immunohistochemical staining demonstrated the expression of OCT4, SOX2, KLF4, and c-MYC on the endothelium and media of lesional vessels and cells within the stroma of the nidus in all 12 AVM tissue samples. ISH and RT-qPCR confirmed transcript expression of all five markers. Western blotting showed protein expression of all markers except NANOG. Immunofluorescence staining demonstrated an OCT4+/SOX2+/KLF4+/c-MYC+ population within the endothelium and media of the lesional vessels and cells within the stroma of the AVM nidus.Conclusions: Our findings may suggest the presence of a primitive population within the AVM nidus. Further investigation may lead to novel therapeutic targeting of this population.

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Stemness-Associated Markers Are Expressed in Extracranial Arteriovenous Malformation

et al. 2021

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“…There is increasing evidence of the presence of ESC-like populations in vascular anomalies ( 22 ), including IH ( 23 ), pyogenic granuloma ( 24 ), venous malformation ( 25 ), verrucous venous malformation ( 27 ), lymphatic malformation ( 28 ), and port-wine stain ( 26 ). We have also demonstrated expression of components of the RAS by the stem cell population within a number of these vascular anomalies ( 24 , 29 , 30 ).…”

Section: Discussionmentioning

confidence: 99%

“…Given that ESCs in other disease states have been shown to be dysfunctional when mTOR is inactivated, as cellular proliferation and pluripotency systems are rendered defective, we speculate that mTOR inactivation may influence pluripotency of cells that express stemness-associated markers in AVM ( 20 , 21 ). There is increasing evidence of the presence of primitive cells within other vascular anomalies ( 22 ), including infantile hemangioma (IH) ( 23 ), pyogenic granuloma ( 24 ), venous malformation ( 25 ), port-wine stain ( 26 ), verrucous venous malformation ( 27 ) and lymphatic malformation ( 28 ). The primitive population in IH ( 29 ), pyogenic granuloma ( 24 ) and venous malformation ( 30 ) have been shown to express components of the renin-angiotensin system (RAS).…”

Section: Introductionmentioning

confidence: 99%

Expression of Cathepsins B, D, and G in Extracranial Arterio-Venous Malformation

et al. 2021

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Objectives: We have previously identified a population of cells that expressed stemness-associated markers in extracranial arterio-venous malformation (AVM) and demonstrated expression of cathepsins B, D, and G on embryonic stem cell (ESC)-like populations in other vascular anomalies. This study investigated the expression of cathepsins B, D, and G, and their localization in relation to this primitive population in extracranial AVM.Methods: Immunohistochemical staining was performed on AVM tissue samples from 13 patients to demonstrate expression of cathepsins B, D, and G. Western blotting was performed on four AVM tissue samples and three AVM-derived primary cell lines to confirm protein expression of cathepsins B and D proteins. RT-qPCR was performed on three AVM-derived primary cell lines to demonstrate transcript expression of cathepsins B, D, and G. Enzymatic activity assays were performed on three AVM-derived primary cell lines to investigate if cathepsins B and D were active. Localization of the cathepsins was investigated using immunofluorescence dual-staining of the cathepsins with the ESC markers OCT4 and SOX2, and mast cells marker chymase on two of the 13 AVM tissue samples.Results: Immunohistochemical staining demonstrated expression of cathepsins B, D, and G in all 13 AVM tissue samples. Western blotting showed expression of cathepsins B and D proteins in all four AVM tissue samples and all three AVM-derived primary cell lines. RT-qPCR demonstrated transcripts of cathepsins B, D, and G in all three AVM-derived primary cell lines. Enzymatic activity assays showed that cathepsins B and D were active. Immunofluorescence staining showed expression of cathepsins B and D on the OCT4+/SOX2+ endothelium and media of the lesional vessels and cells within the stroma in AVM nidus. Cathepsin G was expressed on the chymase+ phenotypic mast cells.Conclusions: This study demonstrated the novel finding of the expression of cathepsins B, D, and G in AVM. Cathepsins B and D were expressed by the primitive population, and cathepsin G was localized to mast cells, within the AVM nidus.

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Oral lymphatic malformations: A multicenter study of 208 cases and literature review

et al. 2021

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Background To evaluate the frequency and analyze demographic and clinical characteristics of individuals with a histopathological diagnosis of oral lymphatic malformations (OLMs). Methods A multicenter study was performed, collecting biopsy record data from a consortium of Brazilian Oral and Maxillofacial Pathology Centers. A review was also conducted to compare this data with cases already available in the literature. Results This study retrieved 208 cases of OLM in the multicenter study and 1035 cases in the literature review. In both, OLMs affected male and female individuals equally, with the most affected site being the tongue. Individuals ≥60 years of age were uncommonly affected. Symptomatic and larger lesions were more commonly reported in the literature review. Conclusions This study comprises the largest sample of OLMs to date. OLMs are rare conditions, without sex predilection. The elderly proved to be less frequently affected, and the tongue is the most commonly affected site.

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Expression of Embryonic Stem Cell Markers in Microcystic Lymphatic Malformation

Cited by 9 publications

References 33 publications

Stemness-Associated Markers Are Expressed in Extracranial Arteriovenous Malformation

Stemness-Associated Markers Are Expressed in Extracranial Arteriovenous Malformation

Expression of Cathepsins B, D, and G in Extracranial Arterio-Venous Malformation

Oral lymphatic malformations: A multicenter study of 208 cases and literature review

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