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1.
Int J Mol Sci ; 24(11)2023 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-37298296

RESUMO

Tumor growth depends on the vascular system, either through the expansion of blood vessels or novel adaptation by tumor cells. One of these novel pathways is vasculogenic mimicry (VM), which is defined as a tumor-provided vascular system apart from endothelial cell-lined vessels, and its origin is partly unknown. It involves highly aggressive tumor cells expressing endothelial cell markers that line the tumor irrigation. VM has been correlated with high tumor grade, cancer cell invasion, cancer cell metastasis, and reduced survival of cancer patients. In this review, we summarize the most relevant studies in the field of angiogenesis and cover the various aspects and functionality of aberrant angiogenesis by tumor cells. We also discuss the intracellular signaling mechanisms involved in the abnormal presence of VE-cadherin (CDH5) and its role in VM formation. Finally, we present the implications for the paradigm of tumor angiogenesis and how targeted therapy and individualized studies can be applied in scientific analysis and clinical settings.


Assuntos
Antígenos CD , Neoplasias , Humanos , Linhagem Celular Tumoral , Antígenos CD/metabolismo , Caderinas/metabolismo , Neovascularização Patológica/metabolismo
2.
Int J Mol Sci ; 23(15)2022 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-35955799

RESUMO

Endoglin (ENG) is a mesenchymal stem cell (MSC) marker typically expressed by active endothelium. This transmembrane glycoprotein is shed by matrix metalloproteinase 14 (MMP14). Our previous work demonstrated potent preclinical activity of first-in-class anti-ENG antibody-drug conjugates as a nascent strategy to eradicate Ewing sarcoma (ES), a devastating rare bone/soft tissue cancer with a putative MSC origin. We also defined a correlation between ENG and MMP14 expression in ES. Herein, we show that ENG expression is significantly associated with a dismal prognosis in a large cohort of ES patients. Moreover, both ENG/MMP14 are frequently expressed in primary ES tumors and metastasis. To deepen in their functional relevance in ES, we conducted transcriptomic and proteomic profiling of in vitro ES models that unveiled a key role of ENG and MMP14 in cell mechano-transduction. Migration and adhesion assays confirmed that loss of ENG disrupts actin filament assembly and filopodia formation, with a concomitant effect on cell spreading. Furthermore, we observed that ENG regulates cell-matrix interaction through activation of focal adhesion signaling and protein kinase C expression. In turn, loss of MMP14 contributed to a more adhesive phenotype of ES cells by modulating the transcriptional extracellular matrix dynamics. Overall, these results suggest that ENG and MMP14 exert a significant role in mediating correct spreading machinery of ES cells, impacting the aggressiveness of the disease.


Assuntos
Neoplasias Ósseas , Endoglina/metabolismo , Sarcoma de Ewing , Neoplasias Ósseas/genética , Endoglina/genética , Humanos , Metaloproteinase 14 da Matriz/genética , Metaloproteinase 14 da Matriz/metabolismo , Proteômica , Receptores de Fatores de Crescimento , Sarcoma de Ewing/patologia , Transdução de Sinais
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