Blockage of αvβ3 integrin in 3D culture of triple-negative breast cancer and endothelial cells inhibits migration and discourages endothelial-to-mesenchymal plasticity

Casali, Bruna Carla; Baptista, Matheus Pintor; Pachane, Bianca Cruz; Cortez, Anelise Abreu; Altei, Wanessa Fernanda; Selistre-de-Araújo, Heloísa Sobreiro

doi:10.1016/j.bbrep.2024.101686

Cited by 3 publications

(2 citation statements)

References 18 publications

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“…Interestingly, BRCA1, a key regulatory gene involved in the cell cycle and DNA repair, is known to interact with and regulate canonical TGF-β signaling [ 41 , 42 ]. Moreover, EndMT is reported in breast cancer [ 43 ], but whether there exists a link between BRCA genes and TGF-β-induced EndMT, particularly in the context of CVDs, remains unknown ( Figure 4 ). Understanding how BRCA1 or BRCA2 mutation-associated genomic instability and tumor heterogeneity contribute towards TGF-β-induced EndMT could pave the way for the development of more effective treatment strategies aimed at targeting not only cancer cells and their tumor microenvironment but also different CVDS in BRCA1/2-mutant individuals.…”

Section: Mechanisms Of Endmtmentioning

confidence: 99%

Endothelial-to-Mesenchymal Transition in Cardiovascular Pathophysiology

Singh,

Bhatt,

Nguyen

et al. 2024

IJMS

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Under different pathophysiological conditions, endothelial cells lose endothelial phenotype and gain mesenchymal cell-like phenotype via a process known as endothelial-to-mesenchymal transition (EndMT). At the molecular level, endothelial cells lose the expression of endothelial cell-specific markers such as CD31/platelet-endothelial cell adhesion molecule, von Willebrand factor, and vascular-endothelial cadherin and gain the expression of mesenchymal cell markers such as α-smooth muscle actin, N-cadherin, vimentin, fibroblast specific protein-1, and collagens. EndMT is induced by numerous different pathways triggered and modulated by multiple different and often redundant mechanisms in a context-dependent manner depending on the pathophysiological status of the cell. EndMT plays an essential role in embryonic development, particularly in atrioventricular valve development; however, EndMT is also implicated in the pathogenesis of several genetically determined and acquired diseases, including malignant, cardiovascular, inflammatory, and fibrotic disorders. Among cardiovascular diseases, aberrant EndMT is reported in atherosclerosis, pulmonary hypertension, valvular disease, fibroelastosis, and cardiac fibrosis. Accordingly, understanding the mechanisms behind the cause and/or effect of EndMT to eventually target EndMT appears to be a promising strategy for treating aberrant EndMT-associated diseases. However, this approach is limited by a lack of precise functional and molecular pathways, causes and/or effects, and a lack of robust animal models and human data about EndMT in different diseases. Here, we review different mechanisms in EndMT and the role of EndMT in various cardiovascular diseases.

show abstract

Section: Mechanisms Of Endmtmentioning

confidence: 99%

Endothelial-to-Mesenchymal Transition in Cardiovascular Pathophysiology

Singh,

Bhatt,

Nguyen

et al. 2024

IJMS

View full text Add to dashboard Cite

show abstract

“…Interestingly, BRCA1, a key regulatory gene involved in the cell cycle and DNA repair, is known to interact with and regulate canonical TGF-β signaling [41,42]. Furthermore, EndMT is reported in breast cancer [43], but whether there exists a link between BRCA genes and TGF-β-induced EndMT particularly in the context of CVDs remains unknown. Understanding how BRCA1 or BRCA2 mutation-associated genomic instability and tumor heterogeneity contributes towards TGF-β-induced EndMT could pave the way for the development of more effective treatment strategies aimed at targeting not only cancer cells and their tumor microenvironment but also different CVDS in BRCA1/2-mutant individuals.…”

Section: Tgf-β Signalingmentioning

confidence: 99%

Endothelial-to-Mesenchymal Transition in Cardiovascular Pathophysiology

Singh,

Bhatt,

Nguyen

et al. 2024

Preprint

View full text Add to dashboard Cite

Under different pathophysiological conditions endothelial cells lose endothelial phenotype and gain mesenchymal cell-like phenotype via a process known as endothelial-to-mesenchymal transition (EndMT). At the molecular level, endothelial cells lose the expression of endothelial cell-specific markers such as CD31/platelet-endothelial cell adhesion molecule, von Willebrand factor, and vascular-endothelial cadherin and gain the expression of mesenchymal cell markers such as α-smooth muscle actin, N-cadherin, vimentin, fibroblast specific protein-1 and collagens. EndMT is induced by numerous different pathways triggered and modulated by multiple different and often redundant mechanisms in a context-dependent manner depending on the pathophysiological status of the cell. EndMT plays an essential role in embryonic development, particularly in atrioventricular valve development, however, EndMT is also implicated in pathogenesis of several genetically determined and acquired diseases including malignant, cardiovascular, inflammatory, and fibrotic disorders. Among cardiovascular diseases aberrant EndMT is reported in atherosclerosis, pulmonary hypertension, valvular disease, fibroelastosis and cardiac fibrosis. Accordingly, understanding the mechanisms behind cause and/or effect of EndMT to eventually target EndMT appears to be a promising strategy to treat aberrant EndMT-associated diseases. However, this approach is limited by a lack of precise functional and molecular pathways, causes and/or effects, and lack of robust animal model and human data about EndMT in different diseases. Here, we review different mechanisms in EndMT and the role of EndMT in various cardiovascular diseases.

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Tumoral hypoxic extracellular vesicles create a protective microenvironment for triple-negative breast cancer

Pachane,

Bottaro,

Machado

et al. 2024

Preprint

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The highly metastatic triple-negative breast cancer (TNBC) relies on its tumor microenvironment (TME) to maintain phenotypic heterogeneity and progression. Extracellular vesicles from hypoxic TNBC were previously shown to aid tumoral invasion but their function in the tumor microenvironment is still unclear. We used a novel method to investigate the TME in vitro called multicellular circulating co-culture, to characterize how TNBC-derived hypoxic EVs (EVh) interfere with tumoral and endothelial cells, fibroblasts, monocytes and macrophages. EVh promoted monocyte differentiation to M2-like macrophages and inhibited macrophage-derived phagocytosis in endothelial and tumoral cells. The protection of endothelial, tumoral and stromal cellular integrity by EVh increased pro-tumoral and pro-angiogenic signaling, collagen matrix synthesis and a potential differentiation to cancer-associated fibroblasts. Our findings highlighted the critical role of EVh in protecting tumor cells, indicating its cooperation towards a protective TME, which was demonstrated by the multicellular circulating co-culture and conventional co-culture protocols, leading to an adequate system with potential for investigating other tumor-related processes, including circulating tumor cells and metastasis.

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Blockage of αvβ3 integrin in 3D culture of triple-negative breast cancer and endothelial cells inhibits migration and discourages endothelial-to-mesenchymal plasticity

Cited by 3 publications

References 18 publications

Endothelial-to-Mesenchymal Transition in Cardiovascular Pathophysiology

Endothelial-to-Mesenchymal Transition in Cardiovascular Pathophysiology

Endothelial-to-Mesenchymal Transition in Cardiovascular Pathophysiology

Tumoral hypoxic extracellular vesicles create a protective microenvironment for triple-negative breast cancer

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