Simultaneously targeting cancer-associated fibroblasts and angiogenic vessel as a treatment for TNBC.
J Exp Med
; 218(4)2021 04 05.
Article
em En
| MEDLINE
| ID: mdl-33561195
ABSTRACT
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 αvß3 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 αvß3. 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Inibidores da Angiogênese
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Neoplasias de Mama Triplo Negativas
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Fibroblastos Associados a Câncer
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Neovascularização Patológica
Tipo de estudo:
Prognostic_studies
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Risk_factors_studies
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
J Exp Med
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Gabão