A 3D multi-cellular tissue model of the human omentum to study the formation of ovarian cancer metastasis

Estermann, Manuela; Coelho, Ruimário Inácio; Jacob, Francis; Huang, Yen‐Lin; Liang, Ching-Yeu; Faia-Torres, Ana Bela; Septiadi, Dedy; Drašler, Barbara; Karakoçak, Bedia Begüm; Dijkhoff, Irini M.; Petri‐Fink, Alke; Heinzelmann‐Schwarz, Viola; Rothen‐Rutishauser, Barbara

doi:10.1016/j.biomaterials.2023.121996

Cited by 4 publications

(1 citation statement)

References 87 publications

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“…The tumor microenvironment (TME) plays a crucial role in modulating drug responses (24). Mesothelial cells represent a major cellular component of the peritoneal microenvironment, the location where EOC cells are predisposed to metastasize (25)(26)(27)(28). Recognizing the importance of mesothelial cells in cancer progression and drug responses, we assessed the efficacy of birinapant in a co-culture assay using aggregates of parental and ΔMSLN OVCAR3 alongside normal immortalized mesothelial cells (MeT5A).…”

Section: Ovarian Cancer Cells With Low Msln Expression Are Selectivel...mentioning

confidence: 99%

SMAC mimetics overcome apoptotic resistance in ovarian cancer through MSLN-TNF alpha axis

Coelho,

Seashore-Ludlow,

Schütz

et al. 2024

Preprint

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Resistance to chemotherapy and PARPi inhibitors remains a critical challenge in the treatment of epithelial ovarian cancer, mainly due to disabled apoptotic responses in tumor cells. Given mesothelin's pivotal role in ovarian cancer and its restricted expression in healthy tissues, we conducted a drug-screening discovery analysis across a range of genetically modified cancer cells to unveil mesothelin's therapeutic impact. We observed enhanced cell death in low mesothelin expressing cancer cells when exposed to a second mitochondria-derived activator of caspases (SMAC) mimetics, and demonstrated a compelling synergy when combined with chemotherapy in ex vivo patient-derived cultures and zebrafish tumor xenografts. Mechanistically, the addition of the SMAC mimetics drug birinapant to either carboplatin or paclitaxel triggered the activation of the Caspase 8-dependent apoptotic program facilitated by TNF alpha signaling. Multimodal analysis of neoadjuvant-treated patient samples further revealed an association between tumor-associated macrophages and the activation of TNF alpha-related pathways. Our proposed bimodal treatment shows promise in enhancing the clinical management of patients by harnessing the potential of SMAC mimetics alongside conventional chemotherapy.

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Section: Ovarian Cancer Cells With Low Msln Expression Are Selectivel...mentioning

confidence: 99%

SMAC mimetics overcome apoptotic resistance in ovarian cancer through MSLN-TNF alpha axis

Coelho,

Seashore-Ludlow,

Schütz

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

Recent applications of three-dimensional bioprinting in drug discovery and development

Yang,

Wang,

Vijayavenkataraman

et al. 2024

Advanced Drug Delivery Reviews

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The high-grade serous ovarian cancer metastasis and chemoresistance in 3D models

Tadić,

Zhang,

Brozovic

2024

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

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A 3D multi-cellular tissue model of the human omentum to study the formation of ovarian cancer metastasis

Cited by 4 publications

References 87 publications

SMAC mimetics overcome apoptotic resistance in ovarian cancer through MSLN-TNF alpha axis

SMAC mimetics overcome apoptotic resistance in ovarian cancer through MSLN-TNF alpha axis

Recent applications of three-dimensional bioprinting in drug discovery and development

The high-grade serous ovarian cancer metastasis and chemoresistance in 3D models

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