Overexpression Prox1 in HemECs resembles Kaposiform hemangioendothelioma and cytotoxicity of sirolimus in vitro.

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.

• Authors: Jing Wang, Qilei Han, Hanlei Yan, Wei Yao, Zuopeng Wang, Kai Li
• Journal: Journal of pediatric surgery (J Pediatr Surg) Vol. 56 Issue 7 Pg. 1203-1210 (Jul 2021) ISSN: 1531-5037 [Electronic] United States
• PMID: 33865602 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Elsevier Inc. All rights reserved.

Chemical References

• Sirolimus

Topics

• Child
• Hemangioendothelioma (drug therapy)
• Humans
• Kasabach-Merritt Syndrome
• Sarcoma, Kaposi
• Sirolimus (pharmacology)