Overexpression Prox1 in HemECs resembles Kaposiform hemangioendothelioma and cytotoxicity of sirolimus in vitro
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Read the article on jpedsurg.org ↗Article · Mar 2021 · 1 min read
In brief
In brief
Researchers established a Prox1-overexpressing cell line that mimics kaposiform hemangioendothelioma behavior, demonstrating increased proliferation and invasion. Sirolimus treatment inhibited cell growth through mTOR pathway blockade and autophagy induction, providing mechanistic insight into its therapeutic efficacy for this rare pediatric vascular tumor.
Written by the GCMD Library team from the article.
Abstract
Background
Kaposiform hemangioendothelioma (KHE) is a rare vascular tumor that occurs in children. Prox1 is a specific lymphatic marker for KHE. We intended to establish a Prox1 transgenic cell line resembling KHE and investigate the mechanism of sirolimus in treating KHE.
Methods
Prox1 was stably expressed in infantile hemangioma cell HemECs. RT-qPCR and Western blot were conducted to measure the expression of target genes. CCK-8, Edu assay, and cell cycle analysis were conducted to detect cell proliferation. Wound healing and transwell assay were used to evaluate cell migration and invasion.
Results
Both mRNA and protein levels of Prox1, LYVE-1, Podoplanin were upregulated in Prox1+ HemECs. An acceleration of cell growth and a rise in migration and invasion were observed with Prox1 overexpression. Sirolimus inhibited cell proliferation, promoted apoptosis and led to G1 phase arrest in Prox1+ HemECs. The expression of p-mTOR, p-4EBP1, and p-P70S6K decreased and the ratio of LC-3 II/LC-3 I elevated after treatment of sirolimus.
Conclusions
Stable overexpression of Prox1 in HemECs induced a lymphatic endothelial reprogramming, and enhanced aggressive biological effects, partly resembled the invasion of KHE, and could serve as a novel model for KHE. Sirolimus may block mTOR-mediated pathways and induced autophagy in KHE.