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JP1 normalizes tumor vasculature to suppress metastasis and facilitate drug delivery by inhibiting IL-8

Tumor vascular normalization prevents tumor cells from breaking through the basement membrane and entering the vasculature, thereby inhibiting metastasis initiation. In this study, we report that the antitumor peptide JP1 regulated mitochondrial metabolic reprogramming through AMPK/FOXO3a/UQCRC2 sig...

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Autores principales: Cui, Jiahua, Che, Zhen, Zou, Lu, Chen, Dongyin, Xie, Zhan, Ding, Kun, Jiang, Huning, Li, Aiping, Zhou, Jianwei, Shu, Yongqian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Clinical Investigation 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10371244/
https://www.ncbi.nlm.nih.gov/pubmed/37192004
http://dx.doi.org/10.1172/jci.insight.161675
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author Cui, Jiahua
Che, Zhen
Zou, Lu
Chen, Dongyin
Xie, Zhan
Ding, Kun
Jiang, Huning
Li, Aiping
Zhou, Jianwei
Shu, Yongqian
author_facet Cui, Jiahua
Che, Zhen
Zou, Lu
Chen, Dongyin
Xie, Zhan
Ding, Kun
Jiang, Huning
Li, Aiping
Zhou, Jianwei
Shu, Yongqian
author_sort Cui, Jiahua
collection PubMed
description Tumor vascular normalization prevents tumor cells from breaking through the basement membrane and entering the vasculature, thereby inhibiting metastasis initiation. In this study, we report that the antitumor peptide JP1 regulated mitochondrial metabolic reprogramming through AMPK/FOXO3a/UQCRC2 signaling, which improved the tumor microenvironment hypoxia. The oxygen-rich tumor microenvironment inhibited the secretion of IL-8 by tumor cells, thereby promoting tumor vascular normalization. The normalized vasculature resulted in mature and regular blood vessels, which made the tumor microenvironment form a benign feedback loop consisting of vascular normalization, sufficient perfusion, and an oxygen-rich microenvironment, prevented tumor cells from entering the vasculature, and inhibited metastasis initiation. Moreover, the combined therapy of JP1 and paclitaxel maintained a certain vascular density in the tumor and promoted tumor vascular normalization, increasing the delivery of oxygen and drugs and enhancing the antitumor effect. Collectively, our work highlights the antitumor peptide JP1 as an inhibitor of metastasis initiation and its mechanism of action.
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spelling pubmed-103712442023-07-27 JP1 normalizes tumor vasculature to suppress metastasis and facilitate drug delivery by inhibiting IL-8 Cui, Jiahua Che, Zhen Zou, Lu Chen, Dongyin Xie, Zhan Ding, Kun Jiang, Huning Li, Aiping Zhou, Jianwei Shu, Yongqian JCI Insight Research Article Tumor vascular normalization prevents tumor cells from breaking through the basement membrane and entering the vasculature, thereby inhibiting metastasis initiation. In this study, we report that the antitumor peptide JP1 regulated mitochondrial metabolic reprogramming through AMPK/FOXO3a/UQCRC2 signaling, which improved the tumor microenvironment hypoxia. The oxygen-rich tumor microenvironment inhibited the secretion of IL-8 by tumor cells, thereby promoting tumor vascular normalization. The normalized vasculature resulted in mature and regular blood vessels, which made the tumor microenvironment form a benign feedback loop consisting of vascular normalization, sufficient perfusion, and an oxygen-rich microenvironment, prevented tumor cells from entering the vasculature, and inhibited metastasis initiation. Moreover, the combined therapy of JP1 and paclitaxel maintained a certain vascular density in the tumor and promoted tumor vascular normalization, increasing the delivery of oxygen and drugs and enhancing the antitumor effect. Collectively, our work highlights the antitumor peptide JP1 as an inhibitor of metastasis initiation and its mechanism of action. American Society for Clinical Investigation 2023-06-22 /pmc/articles/PMC10371244/ /pubmed/37192004 http://dx.doi.org/10.1172/jci.insight.161675 Text en © 2023 Cui et al. https://creativecommons.org/licenses/by/4.0/This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Cui, Jiahua
Che, Zhen
Zou, Lu
Chen, Dongyin
Xie, Zhan
Ding, Kun
Jiang, Huning
Li, Aiping
Zhou, Jianwei
Shu, Yongqian
JP1 normalizes tumor vasculature to suppress metastasis and facilitate drug delivery by inhibiting IL-8
title JP1 normalizes tumor vasculature to suppress metastasis and facilitate drug delivery by inhibiting IL-8
title_full JP1 normalizes tumor vasculature to suppress metastasis and facilitate drug delivery by inhibiting IL-8
title_fullStr JP1 normalizes tumor vasculature to suppress metastasis and facilitate drug delivery by inhibiting IL-8
title_full_unstemmed JP1 normalizes tumor vasculature to suppress metastasis and facilitate drug delivery by inhibiting IL-8
title_short JP1 normalizes tumor vasculature to suppress metastasis and facilitate drug delivery by inhibiting IL-8
title_sort jp1 normalizes tumor vasculature to suppress metastasis and facilitate drug delivery by inhibiting il-8
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10371244/
https://www.ncbi.nlm.nih.gov/pubmed/37192004
http://dx.doi.org/10.1172/jci.insight.161675
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