Methionine aminopeptidase‑2 is a pivotal regulator of vasculogenic mimicry

Shimizu,Shota; Kawahara,Ryota; Simizu,Siro

doi:10.3892/or.2021.8242

Methionine aminopeptidase‑2 is a pivotal regulator of vasculogenic mimicry

Authors:
- Shota Shimizu
- Ryota Kawahara
- Siro Simizu
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Affiliations: Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Yokohama 223‑8522, Japan
Published online on: December 15, 2021 https://doi.org/10.3892/or.2021.8242
Article Number: 31
Copyright: © Shimizu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Vasculogenic mimicry (VM) is the formation of a blood supply system that confers aggressive and metastatic properties to tumors and correlates with a poor prognosis in cancer patients. Thus, the inhibition of VM is considered an effective approach for cancer treatment, although such a mechanism remains poorly described. In the present study, we examined methionine aminopeptidase‑2 (MetAP2), a key factor of angiogenesis, and demonstrated that it is pivotal for VM, using pharmacological and genetic approaches. Fumagillin and TNP‑470, angiogenesis inhibitors that target MetAP2, significantly suppressed VM in various human cancer cell lines. We established MetAP2‑knockout (KO) human fibrosarcoma HT1080 cells using the CRISPR/Cas9 system and found that VM was attenuated in these cells. Furthermore, re‑expression of wild‑type MetAP2 restored VM in the MetAP2‑KO HT1080 cells, but the substitution of D251, a conserved amino acid in MetAP2, failed to rescue the VM. Collectively, our results demonstrate that MetAP2 is critical for VM in human cancer cells and suggest fumagillin and TNP‑470 as potent VM‑suppressing agents.

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