Pathogenesis of infantile haemangioma

Greenberger, Shoshana; Bischoff, Joyce

doi:10.1111/bjd.12435

Cited by 137 publications

(134 citation statements)

References 81 publications

Supporting

Mentioning

127

Contrasting

Unclassified

Order By: Relevance

“…3 Unlike other vascular tumors, IH has a distinctive life cycle that progresses from a phase of rapid proliferation followed by spontaneous involution. During the proliferative phase, IH is composed of disorganized blood vessels and full of multitudinous immature endothelial cells (ECs) 4 and hemangioma stem cells (HemSCs). 5 In contrast, the involuting phase of IH is characterized by vascular tissue replacement by fat and connective tissue.…”

Section: Introductionmentioning

confidence: 99%

Association of ATF4 Expression With Tissue Hypoxia and M2 Macrophage Infiltration in Infantile Hemangioma

Xia

Zhu

Wang

et al. 2017

J Histochem Cytochem.

View full text Add to dashboard Cite

SummaryAccumulating studies have revealed the hypoxic condition and its crucial role in the distinctive progression of infantile hemangioma (IH), the most common benign tumor in infancy. Activating transcription factor 4 (ATF4), an important gene mediating cellular adaptation to various stress signals, could confer a survival advantage for tumor cells under hypoxia and regulate tumor progression. However, the potential role of ATF4 in IH was still unknown. In this study, the expression of hypoxia inducible factor (HIF)-1α, ATF4, and macrophage colony-stimulating factor (M-CSF) in 27 specimens of IH was measured by immunochemistry and double-labeling immunofluorescence, followed by the Spearman rank correlation test. Our results showed that the expression of HIF-1α, ATF4, and M-CSF was significantly upregulated in proliferating IH compared with involuting IH. Meanwhile, HIF-1α and ATF4, in parallel with ATF4 and M-CSF, exhibited positive correlation and synchronous expression. In addition, our in vitro studies demonstrated that hypoxia obviously upregulated the expression of HIF-1α, ATF4, and M-CSF in hemangioma stem cells. Most importantly, their expression was uniformly correlated with the percentage of M2-polarized macrophages in IH. All those results and established evidence indicated that hypoxia-induced ATF4 expression may promote progression of proliferating IH through M-CSF-induced M2-polarized macrophages infiltration. (J Histochem Cytochem 65:285-294, 2017)

show abstract

Section: Introductionmentioning

confidence: 99%

Association of ATF4 Expression With Tissue Hypoxia and M2 Macrophage Infiltration in Infantile Hemangioma

Xia

Zhu

Wang

et al. 2017

J Histochem Cytochem.

View full text Add to dashboard Cite

show abstract

“…Like KS, the vascular lesion infantile hemangioma (IH) develops from dysregulated proliferation of EC (8). The generic ␤-adrenergic antagonist propranolol has been shown recently to be effective against IH and is now a first-line agent for treatment of this vascular lesion (9,10).…”

mentioning

confidence: 99%

Propranolol Decreases Proliferation of Endothelial Cells Transformed by Kaposi's Sarcoma-Associated Herpesvirus and Induces Lytic Viral Gene Expression

McAllister

Hanson

Manion

2015

J Virol

View full text Add to dashboard Cite

Kaposi's sarcoma (KS) is common in Africa, but economic constraints hinder successful treatment in most patients. Propranolol, a generic ␤-adrenergic antagonist, decreased proliferation of KS-associated herpesvirus (KSHV)-infected cells. Downregulation of cyclin A2 and cyclin-dependent kinase 1 (CDK1) recapitulated this phenotype. Additionally, propranolol induced lytic gene expression in association with downregulation of CDK6. Thus, propranolol has diverse effects on KSHV-infected cells, and this generic drug has potential as a therapeutic agent for KS. Kaposi's sarcoma (KS) is a vascular neoplasm initiated by infection of endothelial cells (EC) with KS-associated herpesvirus (KSHV) (1). Infection induces a transformed phenotype typified by anchorage-independent growth, loss of contact inhibition, and upregulation of progrowth pathways. Targeting these altered processes in vitro has identified novel treatment targets (2-5). However, economic constraints prevent clinical translation of many of these observations in areas of high KS burden, so systemic cytotoxic agents, where available, remain the mainstay of KS treatment (6, 7).Like KS, the vascular lesion infantile hemangioma (IH) develops from dysregulated proliferation of EC (8). The generic ␤-adrenergic antagonist propranolol has been shown recently to be effective against IH and is now a first-line agent for treatment of this vascular lesion (9, 10). Given the similarities between KS and IH, we hypothesized that propranolol would decrease proliferation of KSHV-infected EC in a validated in vitro KS model (11). Here we show that postconfluent growth of EC transformed by KSHV requires cyclin-dependent kinase 1 (CDK1) and one of its binding partners, cyclin A2, to complete the S and G 2 -M phases of the cell cycle. Furthermore, we show that induction of KSHV lytic gene expression is associated with downregulation of CDK6. These data suggest that ␤-adrenergic signaling drives KS cell proliferation and suppresses viral reactivation in part by maintaining high levels of cyclin A2 and CDK6, respectively. Additionally, these data identify propranolol as a potential agent for treatment of KS amenable to use in limited-resource settings.Propranolol decreased postconfluent proliferation of KSHV-infected EC. Human lymphatic EC were maintained in endothelial growth medium 2 (EGM-2; Lonza, Allendale, NJ). Transduction of EC with the human papillomavirus E6 and E7

show abstract

“…In addition to the rapid increase in the size of the tumor, other features of the syndrome include the development of a low platelet count, microvascular disease, anemia and blood coagulation dysfunctions (12). In the present study, it was generally considered that vasculogenesis and angiogenesis are involved in the formation of new blood vessels in the hemangioma (13). The potential underlying molecular mechanisms include vascular endothelial growth factor (VEGF) and receptors (VEGFR) (14), angiogenin and receptors (15), the Notch signaling pathway (16), mammalian target of rapamycin (mTOR) signaling pathway (17), β-adrenergic receptors and the renin-angiotensin system (18), among others.…”

Section: Introductionmentioning

confidence: 75%

Artesunate inhibits proliferation and invasion of mouse hemangioendothelioma cells in?vitro and of tumor growth in?vivo

et al. 2017

View full text Add to dashboard Cite

Abstract. Artesunate has been demonstrated to be a novel potential antitumor agent in numerous studies. However, its efficacy in infantile hemangioma is unknown. The aim of the present study was to investigate the role of artesunate in the control of vascular tumor biological behavior and molecular mechanism using mouse hemangioendothelioma endothelial (EOMA) cells and a nude mouse model. Cell viability, apoptosis and invasion were determined by an MTT assay, flow cytometric analysis and Transwell invasion assay, respectively. Reverse transcription-quantitative polymerase chain reaction and western blotting were utilized to examine the expression of genes and proteins. Inoculated EOMA cells were injected into the subcutaneous tissues of nude mice to observe the effect of artesunate therapy on the vascular tumor, an effect that was similar to that of pingyangmycin (PYM). It was identified that artesunate treatment (0-600 µg/ml) inhibited cell growth in a time-and dose-dependent manner. Artesunate at 300 µg/ml significantly reduced the proliferation and invasion of EOMA cells, and significantly decreased the expression of vascular endothelial growth factor (VEGF)-A, VEGFR-1, VEGFR-2 and hypoxia inducible factor-1α over time; caspase-3 was simultaneously upregulated in vitro. Artesunate significantly inhibited tumor growth, and the curative effect was similar to that observed with PYM in vivo. It was concluded that artesunate could effectively inhibit the growth of vascular tumors, and thus could be a novel drug candidate for the treatment of infantile hemangioma.

show abstract

Pathogenesis of infantile haemangioma

Cited by 137 publications

References 81 publications

Association of ATF4 Expression With Tissue Hypoxia and M2 Macrophage Infiltration in Infantile Hemangioma

Association of ATF4 Expression With Tissue Hypoxia and M2 Macrophage Infiltration in Infantile Hemangioma

Propranolol Decreases Proliferation of Endothelial Cells Transformed by Kaposi's Sarcoma-Associated Herpesvirus and Induces Lytic Viral Gene Expression

Artesunate inhibits proliferation and invasion of mouse hemangioendothelioma cells in?vitro and of tumor growth in?vivo

Contact Info

Product

Resources

About