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Cooperation Between Cancer and Fibroblasts in Vascular Mimicry and N2-Type Neutrophil Recruitment via Notch2–Jagged1 Interaction in Lung Cancer

BACKGROUND: Angiogenesis is required for tumor development and metastasis, which is a major part in a pro-tumor microenvironment. Vascular mimicry (VM) is a process in which cancer cells, rather than endothelia, create an alternative perfusion system to support the tumor progression. OBJECTIVES: To...

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Autores principales: Tsai, Ying-Ming, Wu, Kuan-Li, Liu, Yu-Wei, Chang, Wei-An, Huang, Yung-Chi, Chang, Chao-Yuan, Tsai, Pei-Hsun, Liao, Szi-Hui, Hung, Jen-Yu, Hsu, Ya-Ling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415962/
https://www.ncbi.nlm.nih.gov/pubmed/34485133
http://dx.doi.org/10.3389/fonc.2021.696931
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author Tsai, Ying-Ming
Wu, Kuan-Li
Liu, Yu-Wei
Chang, Wei-An
Huang, Yung-Chi
Chang, Chao-Yuan
Tsai, Pei-Hsun
Liao, Szi-Hui
Hung, Jen-Yu
Hsu, Ya-Ling
author_facet Tsai, Ying-Ming
Wu, Kuan-Li
Liu, Yu-Wei
Chang, Wei-An
Huang, Yung-Chi
Chang, Chao-Yuan
Tsai, Pei-Hsun
Liao, Szi-Hui
Hung, Jen-Yu
Hsu, Ya-Ling
author_sort Tsai, Ying-Ming
collection PubMed
description BACKGROUND: Angiogenesis is required for tumor development and metastasis, which is a major part in a pro-tumor microenvironment. Vascular mimicry (VM) is a process in which cancer cells, rather than endothelia, create an alternative perfusion system to support the tumor progression. OBJECTIVES: To validate the role of VM and to develop a strategy to inhibit angiogenesis in lung cancer. METHODS: In this study, we utilized lung cancer samples to verify the existence of VM and conducted several experimental methods to elucidate the molecular pathways. RESULTS: H1299 and CL1-0 lung cancer cells were unable to form capillary-like structures. VM formation was induced by cancer-associated fibroblast (CAFs) in both in vitro and in vivo experiments. Notch2–Jagged1 cell–cell contact between cancer cells and CAFs contributes to the formation of VM networks, supported by Notch intracellular domain (NICD) 2 nuclear translocation and N2ICD target gene upregulated in lung cancer cells mixed with CAFs. The polarization of tumor-promoting N2-type neutrophil was increased by VM networks consisting of CAF and cancer cells. The intravasation of cancer cells and N2-type neutrophils were increased because of the loose junctions of VM. Disruption of cancer cell–CAF connections by a γ‐secretase inhibitor enforced the anticancer effect of anti‐vascular endothelial growth factor antibodies in a mouse model. CONCLUSION: This study provides the first evidence that CAFs induce lung cancer to create vascular-like networks. These findings suggest a therapeutic opportunity for improving antiangiogenesis therapy in lung cancer.
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spelling pubmed-84159622021-09-04 Cooperation Between Cancer and Fibroblasts in Vascular Mimicry and N2-Type Neutrophil Recruitment via Notch2–Jagged1 Interaction in Lung Cancer Tsai, Ying-Ming Wu, Kuan-Li Liu, Yu-Wei Chang, Wei-An Huang, Yung-Chi Chang, Chao-Yuan Tsai, Pei-Hsun Liao, Szi-Hui Hung, Jen-Yu Hsu, Ya-Ling Front Oncol Oncology BACKGROUND: Angiogenesis is required for tumor development and metastasis, which is a major part in a pro-tumor microenvironment. Vascular mimicry (VM) is a process in which cancer cells, rather than endothelia, create an alternative perfusion system to support the tumor progression. OBJECTIVES: To validate the role of VM and to develop a strategy to inhibit angiogenesis in lung cancer. METHODS: In this study, we utilized lung cancer samples to verify the existence of VM and conducted several experimental methods to elucidate the molecular pathways. RESULTS: H1299 and CL1-0 lung cancer cells were unable to form capillary-like structures. VM formation was induced by cancer-associated fibroblast (CAFs) in both in vitro and in vivo experiments. Notch2–Jagged1 cell–cell contact between cancer cells and CAFs contributes to the formation of VM networks, supported by Notch intracellular domain (NICD) 2 nuclear translocation and N2ICD target gene upregulated in lung cancer cells mixed with CAFs. The polarization of tumor-promoting N2-type neutrophil was increased by VM networks consisting of CAF and cancer cells. The intravasation of cancer cells and N2-type neutrophils were increased because of the loose junctions of VM. Disruption of cancer cell–CAF connections by a γ‐secretase inhibitor enforced the anticancer effect of anti‐vascular endothelial growth factor antibodies in a mouse model. CONCLUSION: This study provides the first evidence that CAFs induce lung cancer to create vascular-like networks. These findings suggest a therapeutic opportunity for improving antiangiogenesis therapy in lung cancer. Frontiers Media S.A. 2021-08-17 /pmc/articles/PMC8415962/ /pubmed/34485133 http://dx.doi.org/10.3389/fonc.2021.696931 Text en Copyright © 2021 Tsai, Wu, Liu, Chang, Huang, Chang, Tsai, Liao, Hung and Hsu https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Tsai, Ying-Ming
Wu, Kuan-Li
Liu, Yu-Wei
Chang, Wei-An
Huang, Yung-Chi
Chang, Chao-Yuan
Tsai, Pei-Hsun
Liao, Szi-Hui
Hung, Jen-Yu
Hsu, Ya-Ling
Cooperation Between Cancer and Fibroblasts in Vascular Mimicry and N2-Type Neutrophil Recruitment via Notch2–Jagged1 Interaction in Lung Cancer
title Cooperation Between Cancer and Fibroblasts in Vascular Mimicry and N2-Type Neutrophil Recruitment via Notch2–Jagged1 Interaction in Lung Cancer
title_full Cooperation Between Cancer and Fibroblasts in Vascular Mimicry and N2-Type Neutrophil Recruitment via Notch2–Jagged1 Interaction in Lung Cancer
title_fullStr Cooperation Between Cancer and Fibroblasts in Vascular Mimicry and N2-Type Neutrophil Recruitment via Notch2–Jagged1 Interaction in Lung Cancer
title_full_unstemmed Cooperation Between Cancer and Fibroblasts in Vascular Mimicry and N2-Type Neutrophil Recruitment via Notch2–Jagged1 Interaction in Lung Cancer
title_short Cooperation Between Cancer and Fibroblasts in Vascular Mimicry and N2-Type Neutrophil Recruitment via Notch2–Jagged1 Interaction in Lung Cancer
title_sort cooperation between cancer and fibroblasts in vascular mimicry and n2-type neutrophil recruitment via notch2–jagged1 interaction in lung cancer
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415962/
https://www.ncbi.nlm.nih.gov/pubmed/34485133
http://dx.doi.org/10.3389/fonc.2021.696931
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