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Simultaneously targeting cancer-associated fibroblasts and angiogenic vessel as a treatment for TNBC

Fibrotic tumor stroma plays an important role in facilitating triple-negative breast cancer (TNBC) progression and chemotherapeutic resistance. We previously reported a rationally designed protein (ProAgio) that targets integrin α(v)β(3) at a novel site. ProAgio induces apoptosis via the integrin. C...

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Autores principales: Sharma, Malvika, Turaga, Ravi Chakra, Yuan, Yi, Satyanarayana, Ganesh, Mishra, Falguni, Bian, Zhen, Liu, Wei, Sun, Li, Yang, Jenny, Liu, Zhi-Ren
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876552/
https://www.ncbi.nlm.nih.gov/pubmed/33561195
http://dx.doi.org/10.1084/jem.20200712
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author Sharma, Malvika
Turaga, Ravi Chakra
Yuan, Yi
Satyanarayana, Ganesh
Mishra, Falguni
Bian, Zhen
Liu, Wei
Sun, Li
Yang, Jenny
Liu, Zhi-Ren
author_facet Sharma, Malvika
Turaga, Ravi Chakra
Yuan, Yi
Satyanarayana, Ganesh
Mishra, Falguni
Bian, Zhen
Liu, Wei
Sun, Li
Yang, Jenny
Liu, Zhi-Ren
author_sort Sharma, Malvika
collection PubMed
description Fibrotic tumor stroma plays an important role in facilitating triple-negative breast cancer (TNBC) progression and chemotherapeutic resistance. We previously reported a rationally designed protein (ProAgio) that targets integrin α(v)β(3) at a novel site. ProAgio induces apoptosis via the integrin. Cancer-associated fibroblasts (CAFs) and angiogenic endothelial cells (aECs) in TNBC tumor express high levels of integrin α(v)β(3.) ProAgio effectively induces apoptosis in CAFs and aECs. The depletion of CAFs by ProAgio reduces intratumoral collagen and decreases growth factors released from CAFs in the tumor, resulting in decreased cancer cell proliferation and apoptotic resistance. ProAgio also eliminates leaky tumor angiogenic vessels, which consequently reduces tumor hypoxia and improves drug delivery. The depletion of CAFs and reduction in hypoxia by ProAgio decreases lysyl oxidase (LOX) secretion, which may play a role in the reduction of metastasis. ProAgio stand-alone or in combination with a chemotherapeutic agent provides survival benefit in TNBC murine models, highlighting the therapeutic potential of ProAgio as a treatment strategy.
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spelling pubmed-78765522021-10-05 Simultaneously targeting cancer-associated fibroblasts and angiogenic vessel as a treatment for TNBC Sharma, Malvika Turaga, Ravi Chakra Yuan, Yi Satyanarayana, Ganesh Mishra, Falguni Bian, Zhen Liu, Wei Sun, Li Yang, Jenny Liu, Zhi-Ren J Exp Med Article Fibrotic tumor stroma plays an important role in facilitating triple-negative breast cancer (TNBC) progression and chemotherapeutic resistance. We previously reported a rationally designed protein (ProAgio) that targets integrin α(v)β(3) at a novel site. ProAgio induces apoptosis via the integrin. Cancer-associated fibroblasts (CAFs) and angiogenic endothelial cells (aECs) in TNBC tumor express high levels of integrin α(v)β(3.) ProAgio effectively induces apoptosis in CAFs and aECs. The depletion of CAFs by ProAgio reduces intratumoral collagen and decreases growth factors released from CAFs in the tumor, resulting in decreased cancer cell proliferation and apoptotic resistance. ProAgio also eliminates leaky tumor angiogenic vessels, which consequently reduces tumor hypoxia and improves drug delivery. The depletion of CAFs and reduction in hypoxia by ProAgio decreases lysyl oxidase (LOX) secretion, which may play a role in the reduction of metastasis. ProAgio stand-alone or in combination with a chemotherapeutic agent provides survival benefit in TNBC murine models, highlighting the therapeutic potential of ProAgio as a treatment strategy. Rockefeller University Press 2021-02-09 /pmc/articles/PMC7876552/ /pubmed/33561195 http://dx.doi.org/10.1084/jem.20200712 Text en © 2021 Sharma et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Sharma, Malvika
Turaga, Ravi Chakra
Yuan, Yi
Satyanarayana, Ganesh
Mishra, Falguni
Bian, Zhen
Liu, Wei
Sun, Li
Yang, Jenny
Liu, Zhi-Ren
Simultaneously targeting cancer-associated fibroblasts and angiogenic vessel as a treatment for TNBC
title Simultaneously targeting cancer-associated fibroblasts and angiogenic vessel as a treatment for TNBC
title_full Simultaneously targeting cancer-associated fibroblasts and angiogenic vessel as a treatment for TNBC
title_fullStr Simultaneously targeting cancer-associated fibroblasts and angiogenic vessel as a treatment for TNBC
title_full_unstemmed Simultaneously targeting cancer-associated fibroblasts and angiogenic vessel as a treatment for TNBC
title_short Simultaneously targeting cancer-associated fibroblasts and angiogenic vessel as a treatment for TNBC
title_sort simultaneously targeting cancer-associated fibroblasts and angiogenic vessel as a treatment for tnbc
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876552/
https://www.ncbi.nlm.nih.gov/pubmed/33561195
http://dx.doi.org/10.1084/jem.20200712
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