Abstract
Hemangioendothelioma (HE) is a type of angiomatous lesions that features endothelial cell proliferation. Understanding the mechanisms orchestrating HE angiogenesis can provide therapeutic insights. It has been shown that platelets can support normal and malignant endothelial cells during angiogenesis. Using the mouse endothelial-derived EOMA cell line as a model of HE, we explored the regulatory effect of platelets. We found that platelets stimulated EOMA proliferation but did not mitigate apoptosis. Furthermore, direct platelet-EOMA cell contact was required and the proliferation was mediated via integrin β3/Akt signaling in EOMA cells. SiRNA knockdown of integrin β3 and inhibition of Akt activity significantly abolished platelet-induced EOMA cell proliferation in vitro and tumor development in vivo. These results provide a new mechanism by which platelets support HE progression and suggest integrin β3 as a potential target to treat HE.
Highlights
Hemangioendothelioma (HE) is a type of angiomatous lesions that features endothelial cell proliferation
Using the well-established Annexin V/propidium iodide (PI) assay, we evaluated the apoptosis of EOMA cells and mouse brain microvascular endothelial cells (MBMECs) co-cultured with platelets
Pre-treatment with the integrin-linked kinase (ILK)-specific inhibitor, QLT0267, prevented platelet-induced Akt phosphorylation (Fig. 5h). These results indicate the involvement of integrin β3/ILK signaling in platelet-associated Akt activation in EOMA cells
Summary
Hemangioendothelioma (HE) is a type of angiomatous lesions that features endothelial cell proliferation. Using the mouse endothelial-derived EOMA cell line as a model of HE, we explored the regulatory effect of platelets. SiRNA knockdown of integrin β3 and inhibition of Akt activity significantly abolished platelet-induced EOMA cell proliferation in vitro and tumor development in vivo. These results provide a new mechanism by which platelets support HE progression and suggest integrin β3 as a potential target to treat HE. To investigate the therapeutic targets of HE, the EOMA endothelial cell line, derived from a mixed HE arising in an adult mouse, was developed as a model of HE4. In the present study we utilized the EOMA cell line, a well-recognized cell model of HE, to investigate the influence of platelets on HE development. This study illustrates the importance of platelets upon HE progression and suggests potential avenues for the therapeutic treatment of HE development
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