Regulatory mechanisms and therapeutic targeting of vasculogenic mimicry in hepatocellular carcinoma

Ning Zheng; Shaoqin Zhang; Wenda Wu; Nan Zhang; Jichuang Wang

doi:10.1016/j.phrs.2021.105507

Regulatory mechanisms and therapeutic targeting of vasculogenic mimicry in hepatocellular carcinoma

Pharmacol Res. 2021 Apr:166:105507. doi: 10.1016/j.phrs.2021.105507. Epub 2021 Feb 18.

Authors

Ning Zheng¹, Shaoqin Zhang², Wenda Wu², Nan Zhang², Jichuang Wang³

Affiliations

¹ Department of Pharmacology, The School of Pharmacy, Fujian Provincial Key Laboratory of Natural Medicine Pharmacology, Fujian Medical University, Fuzhou, Fujian 350122, China.
² Fujian Key Laboratory for Translational Research in Cancer and Neurodegenerative Diseases, Institute for Translational Medicine, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian 350122, China.
³ Fujian Key Laboratory for Translational Research in Cancer and Neurodegenerative Diseases, Institute for Translational Medicine, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian 350122, China. Electronic address: [email protected].

PMID: 33610718
DOI: 10.1016/j.phrs.2021.105507

Abstract

Hepatocellular carcinoma (HCC) is a typical hyper-vascular solid tumor; aberrantly rich in tumor vascular network contributes to its malignancy. Conventional anti-angiogenic therapies seem promising but transitory and incomplete efficacy on HCC. Vasculogenic mimicry (VM) is one of functional microcirculation patterns independent of endothelial vessels which describes the plasticity of highly aggressive tumor cells to form vasculogenic-like networks providing sufficient blood supply for tumor growth and metastasis. As a pivotal alternative mechanism for tumor vascularization when tumor cells undergo lack of oxygen and nutrients, VM has an association with the malignant phenotype and poor clinical outcome for HCC, and may challenge the classic anti-angiogenic treatment of HCC. Current studies have contributed numerous findings illustrating the underlying molecular mechanisms and signaling pathways supporting VM in HCC. In this review, we summarize the correlation between epithelial-mesenchymal transition (EMT), cancer stem cells (CSCs) and VM, the role of hypoxia and extracellular matrix remodeling in VM, the involvement of adjacent non-cancerous cells, cytokines and growth factors in VM, as well as the regulatory influence of non-coding RNAs on VM in HCC. Moreover, we discuss the clinical significance of VM in practice and the potential therapeutic strategies targeting VM for HCC. A better understanding of the mechanism underlying VM formation in HCC may optimize anti-angiogenic treatment modalities for HCC.

Keywords: Arsenic trioxide (PubChem CID: 14888); Cancer stem cells; Curcumin (PubChem CID: 969516); Doxycycline (PubChem CID: 54671203); Epithelial-mesenchymal transition; Fasudil (PubChem CID: 3547); Hepatocellular carcinoma; Incarvine C (PubChem CID: 11222122); Melittin (PubChem CID: 16133648); Molecular signaling and anti-VM therapy; NVP-BEP800 (PubChem CID: 25210273); Non-coding RNAs; Polyphyllin I (PubChem CID: 11018329); Regorafenib (PubChem CID: 11167602); Vasculogenic mimicry.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Angiogenesis Inhibitors / pharmacology
Angiogenesis Inhibitors / therapeutic use*
Animals
Carcinoma, Hepatocellular / blood supply*
Carcinoma, Hepatocellular / drug therapy*
Carcinoma, Hepatocellular / metabolism
Carcinoma, Hepatocellular / pathology
Epithelial-Mesenchymal Transition / drug effects
Humans
Liver Neoplasms / blood supply*
Liver Neoplasms / drug therapy*
Liver Neoplasms / metabolism
Liver Neoplasms / pathology
Molecular Targeted Therapy
Neovascularization, Pathologic / drug therapy*
Neovascularization, Pathologic / metabolism
Neovascularization, Pathologic / pathology
Signal Transduction / drug effects

Substances

Angiogenesis Inhibitors