2. Academic Validation
  3. The Angiotensin-Converting Enzyme Inhibitory State Promotes the Transformation of Non-Small Cell Lung Cancer Blood Supply Pattern Toward Vasculogenic Mimicry Formation

The Angiotensin-Converting Enzyme Inhibitory State Promotes the Transformation of Non-Small Cell Lung Cancer Blood Supply Pattern Toward Vasculogenic Mimicry Formation

  • Front Oncol. 2021 Jun 16;11:663671. doi: 10.3389/fonc.2021.663671.
Kandi Xu 1 2,  Huize Han 3,  Yexin Luo 4,  Hong Ye 5,  Hongxia Lin 1 2,  Lei Ni 1 2
Affiliations

Affiliations

  • 1 Department of Respiration and Critical Care Diseases, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • 2 Institute of Respiratory Diseases, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • 3 Respiratory and Critical Care Center, Shanghai East Hospital, Tongji University, Shanghai, China.
  • 4 First Clinical Medical College, Anhui Medical University, Anhui, China.
  • 5 School of Foreign Studies, Anhui University, Anhui, China.
PMID: 34221978 DOI: 10.3389/fonc.2021.663671
Abstract

Tumor microenvironment plays an important role in tumor proliferation, metastasis, and angiogenesis. Local Ras is a key factor to tumor proliferation and metastasis in NSCLC microenvironment, but its role on angiogenesis and VM formation remains unclear. Although overwhelming majority of previous studies suggested that VM is well established in aggressive tumor and facilitates tumor growth and metastasis, we put forward different views from another angle. We proved that status of tumor blood supply patterns, including VM channels and endothelial vessels, can dynamically exchange with each other along with local Ras fluctuations in microenvironment. Quantitatively, ACE2/ACEI promotes VM formation via Nodal/Notch4 activation; while structurally, ACE2/ACEI leads to a strong and solid structure of VM via inhibition of VE-cadherin internalization. These changes induced by ACE2/ACEI relate to relatively low metastasis rate and comforting prognoses of NSCLC patients.

Keywords

Notch4; VE-cadherin; angiotensin-converting enzyme 2; nodal; non-small cell lung cancer; renin-angiotensin system; vasculogenic mimicry.

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