Infantile Hemangiomas Exhibit Neural Crest and Pericyte Markers

Itinteang, Tinte; Davis, Paul F.; Tan, Swee T.

doi:10.1097/sap.0000000000000426

Cited by 3 publications

(2 citation statements)

References 7 publications

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“…A recent report has shown that an abnormal formation of the NC is a causative factor in the development of haemangiomas, which are endothelial cell tumors (Itinteang et al, ). Additionally, there is increasing evidence that infantile haemangioma (IH) is a disorder of aberrant proliferation and differentiation of primitive mesoderm and NC‐derived cells.…”

Section: Chemical Agentsmentioning

confidence: 99%

The role of teratogens in neural crest development

Cerrizuela

Vega-Lopez

Aybar

2020

Birth Defects Research

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The neural crest (NC), discovered by Wilhelm His 150 years ago, gives rise to a multipotent migratory embryonic cell population that generates a remarkably diverse and important array of cell types during the development of the vertebrate embryo. These cells originate in the neural plate border (NPB), which is the ectoderm between the neural plate and the epidermis. They give rise to the neurons and glia of the peripheral nervous system, melanocytes, chondrocytes, smooth muscle cells, odontoblasts and neuroendocrine cells, among others. Neurocristopathies are a class of congenital diseases resulting from the abnormal induction, specification, migration, differentiation or death of NC cells (NCCs) during embryonic development and have an important medical and societal impact. In general, congenital defects affect an appreciable percentage of newborns worldwide. Some of these defects are caused by teratogens, which are agents that negatively impact the formation of tissues and organs during development. In this review, we will discuss the teratogens linked to the development of many birth defects, with a strong focus on those that specifically affect the development of the NC, thereby producing neurocristopathies.Although increasing attention is being paid to the effect of teratogens on embryonic development in general, there is a strong need to critically evaluate the specific role of these agents in NC development. Therefore, increased understanding of the role of these factors in NC development will contribute to the planning of strategies aimed at the prevention and treatment of human neurocristopathies, whose etiology was previously not considered.

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Section: Chemical Agentsmentioning

confidence: 99%

The role of teratogens in neural crest development

Cerrizuela

Vega-Lopez

Aybar

2020

Birth Defects Research

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“…As stem/progenitor cells, angiogenesis and pre-existing vessels are sufficient to induce vasculogenesis, HA proliferation is likely to occur (3). HA-derived endothelial cells (HDECs), progenitor/stem cells and perivascular cells are three well-characterized cells isolated from Has (4,5). However, the mechanisms underlying the development and progression of HA are not yet fully understood.…”

Section: Introductionmentioning

confidence: 99%

miR‑4458 directly targets IGF1R to inhibit cell proliferation and promote apoptosis in hemangioma

Tang

et al. 2020

Exp Ther Med

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Hemangiomas (HAs) are benign neoplasms of the vasculature. MicroRNA-4458 (miR-4458) has been reported to function as a tumor suppressor in multiple malignancies, but its biological function in HAs remains unknown. In the present study, the potential role of miR-4458 in HA-derived endothelial cells (HDECs) was investigated. Firstly, reverse-transcription-quantitative PCR analysis was used to confirm the expression of miR-4458 in HDECs following transfection with miR-4458 mimics or inhibitor. Subsequently, MTT and EdU assays were performed and subsequently determined that miR-4458 overexpression significantly inhibited proliferation, and knockdown promoted cell proliferation in HDECs. Flow cytometry analysis revealed that miR-4458 overexpression induced cell cycle arrest, whereas knockdown reversed G0/G1 phase arrest and apoptosis. Furthermore, insulin-like growth factor 1 receptor (IGF1R) was identified as a target of miR-4458. IGF1R knockdown enhanced the effects of miR-4458 on cell proliferation, cell cycle G0/G1 phase arrest and apoptosis in HDECs. Taken together, the results revealed that miR-4458 targeting of IGF1R may serve as a novel therapeutic strategy for treating patients with HAs.

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Cell Populations Expressing Stemness-Associated Markers in Vascular Anomalies

et al. 2021

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Treatment of vascular anomalies (VAs) is mostly empirical and, in many instances unsatisfactory, as the pathogeneses of these heterogeneous conditions remain largely unknown. There is emerging evidence of the presence of cell populations expressing stemness-associated markers within many types of vascular tumors and vascular malformations. The presence of these populations in VAs is supported, in part, by the observed clinical effect of the mTOR inhibitor, sirolimus, that regulates differentiation of embryonic stem cells (ESCs). The discovery of the central role of the renin-angiotensin system (RAS) in regulating stem cells in infantile hemangioma (IH) provides a plausible explanation for its spontaneous and accelerated involution induced by β-blockers and ACE inhibitors. Recent work on targeting IH stem cells by inhibiting the transcription factor SOX18 using the stereoisomer R(+) propranolol, independent of β-adrenergic blockade, opens up exciting opportunities for novel treatment of IH without the β-adrenergic blockade-related side effects. Gene mutations have been identified in several VAs, involving mainly the PI3K/AKT/mTOR and/or the Ras/RAF/MEK/ERK pathways. Existing cancer therapies that target these pathways engenders the exciting possibility of repurposing these agents for challenging VAs, with early results demonstrating clinical efficacy. However, there are several shortcomings with this approach, including the treatment cost, side effects, emergence of treatment resistance and unknown long-term effects in young patients. The presence of populations expressing stemness-associated markers, including transcription factors involved in the generation of induced pluripotent stem cells (iPSCs), in different types of VAs, suggests the possible role of stem cell pathways in their pathogenesis. Components of the RAS are expressed by cell populations expressing stemness-associated markers in different types of VAs. The gene mutations affecting the PI3K/AKT/mTOR and/or the Ras/RAF/MEK/ERK pathways interact with different components of the RAS, which may influence cell populations expressing stemness-associated markers within VAs. The potential of targeting these populations by manipulating the RAS using repurposed, low-cost and commonly available oral medications, warrants further investigation. This review presents the accumulating evidence demonstrating the presence of stemness-associated markers in VAs, their expression of the RAS, and their interaction with gene mutations affecting the PI3K/AKT/mTOR and/or the Ras/RAF/MEK/ERK pathways, in the pathogenesis of VAs.

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Infantile Hemangiomas Exhibit Neural Crest and Pericyte Markers

Cited by 3 publications

References 7 publications

The role of teratogens in neural crest development

The role of teratogens in neural crest development

miR‑4458 directly targets IGF1R to inhibit cell proliferation and promote apoptosis in hemangioma

Cell Populations Expressing Stemness-Associated Markers in Vascular Anomalies

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