A novel patient-derived xenograft model for claudin-low triple-negative breast cancer

Matossian, Margarite D.; Burks, Hope E.; Bowles, Annie C.; Elliott, Steven; Hoang, Van T.; Sabol, Rachel A.; Pashos, Nicholas C.; O’Donnell, Benjamen T.; Miller, Kristin S.; Wahba, Bahia; Bunnell, Bruce A.; Moroz, Krzysztof; Zea, Arnold H.; Jones, Steven; Ochoa, Augusto C.; Al-Khami, Amir A.; Hossain, Fokhrul; Riker, Adam I.; Rhodes, Lyndsay V.; Martin, Elizabeth C.; Miele, Lucio; Burow, Matthew E.; Collins‐Burow, Bridgette M.

doi:10.1007/s10549-018-4685-2

Cited by 23 publications

(20 citation statements)

References 42 publications

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“…However, because genomic differences in TU-BcX- 2O0 treated explants most recapitulated cell line effects compared to our other TNBC models, we chose to interrogate TU-BcX-2O0 as the translational model in this study. We have previously described TU- BcX-2O0 as a claudin-low TNBC PDX model [ 24 ].…”

Section: Resultsmentioning

confidence: 99%

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Panobinostat suppresses the mesenchymal phenotype in a novel claudin-low triple negative patient-derived breast cancer model

et al. 2018

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Claudin-low triple negative breast cancer (CL-TNBC) is a clinically aggressive molecular TNBC subtype characterized by a propensity to metastasize, recur and acquire chemoresistance. CL-TNBC has a diverse intra- and extracellular composition and microenvironment, and currently there are no clinically approved targeted therapies. Histone deacetylase inhibitors (HDACi) have been investigated as therapeutic agents targeting invasive TNBC phenotypes. However, further studies are required to evaluate HDAC inhibition in CL-TNBC. Here, we utilize a novel CL- TNBC patient-derived xenograft model to study the various and diverse therapeutic potential targets within CL-TNBC tumors. To evaluate effects of the pan-HDACi panobinostat on metastasis and the mesenchymal phenotype of CL-TNBC, we utilize immunohistochemistry staining and qRT-PCR in in vitro, ex vivo and in vivo studies. Further, we evaluate pan-HDAC inhibition on stem-like subpopulations using 3D mammosphere culture techniques and quantification. Finally, we show that pan- HDACi suppresses collagen expression in CL-TNBC. In this study, we provide evidence that pan-HDAC inhibition has effects on various components of the CL-TNBC subtype, and we demonstrate the potential of our novel CL-TNBC PDX model in therapeutic discovery research.

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Section: Resultsmentioning

confidence: 99%

“…Dissecting the various aspects of PDX breast tumors provides the ideal model to study how HDAC inhibitors, or other small molecule inhibitors, affect different microenvironment components in a translational setting. In our investigation, we utilize a novel CL-TNBC PDX model established in our laboratory [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

Panobinostat suppresses the mesenchymal phenotype in a novel claudin-low triple negative patient-derived breast cancer model

et al. 2018

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“…The PDX breast cancer models are being deployed in studies evaluating tumor drug response at the physiological and transcriptomic levels. 13,[43][44][45] Nevertheless, the logistics of tissue processing and storage within a relatively short time frame are roadblocks to the widespread adoption of PDX as an avenue for individualized medical therapy and patient stratification in clinical trials.…”

Section: Breast Cancer Cells and 3d Modelsmentioning

confidence: 99%

“…3,10 While there have been recent advances in the generation of patientderived xenograft (PDX) models, these continue to require immunodeficient mice as in vivo hosts for both expansion and propagation-based studies. [11][12][13] Studies have shown that both the ECM and murine host system impact the pathophysiology of human-derived breast cancer cells, thereby demonstrating a need for an alternative approach that is less dependent on the mouse. 14,15 Based on the principles introduced by Bissell, Griffith, Prestwich, and their colleagues, [4][5][6]16,17 an ideal human breast cancer MPS model would possess the above characteristics regarding performance consistency, ease of use, and amenability to highthroughput formats, in addition to the following attributes:…”

Section: Introductionmentioning

confidence: 99%

Breast Cancer Reconstruction: Design Criteria for a Humanized Microphysiological System

Frazier¹,

Williams

Duplessis

et al. 2021

Tissue Engineering Part A

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International regulatory agencies such as the Food and Drug Administration have mandated that the scientific community develop humanized microphysiological systems (MPS) as an in vitro alternative to animal models in the near future. While the breast cancer research community has long appreciated the importance of threedimensional growth dynamics in their experimental models, there are remaining obstacles preventing a full conversion to humanized MPS for drug discovery and pathophysiological studies. This perspective evaluates the current status of human tissue-derived cells and scaffolds as building blocks for an ''idealized'' breast cancer MPS based on bioengineering design principles. It considers the utility of adipose tissue as a potential source of endothelial, lymphohematopoietic, and stromal cells for the support of breast cancer epithelial cells. The relative merits of potential MPS scaffolds derived from adipose tissue, blood components, and synthetic biomaterials is evaluated relative to the current ''gold standard'' material, Matrigel, a murine chondrosarcomaderived basement membrane-enriched hydrogel. The advantages and limitations of a humanized breast cancer MPS are discussed in the context of in-process and destructive read-out assays.

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“…For example, Lehmann et al have proposed four TNBC tumor specific subtypes referred to as basal like (BL)1, BL2, mesenchymal and luminal androgen receptor (LAR) ( 80 ). Basal-like tumors that are triple negative and have low expression of luminal differentiation markers, high expression of genes involved with the epithelial-to-mesenchymal transition (EMT) and immune response, and are enriched with cancer stem cells are referred to as claudin-low (CL) TNBC ( 81 ). One study demonstrated supplementation with EPA+DHA (0.025%) significantly decreased growth of models of both claudin low (CL) and basal-like (BL) murine mammary tumors in mice fed an obesogenic diet (60% fat) ( 48 ).…”

Section: Fish Oil and Tnbc: Reviewmentioning

confidence: 99%

Do Olive and Fish Oils of the Mediterranean Diet Have a Role in Triple Negative Breast Cancer Prevention and Therapy? An Exploration of Evidence in Cells and Animal Models

et al. 2020

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Breast cancer is the most common malignancy and cause of cancer-related mortality among women worldwide. Triple negative breast cancers (TNBC) are the most aggressive and lethal of the breast cancer molecular subtypes, due in part to a poor understanding of TNBC etiology and lack of targeted therapeutics. Despite advances in the clinical management of TNBC, optimal treatment regimens remain elusive. Thus, identifying interventional approaches that suppress the initiation and progression of TNBC, while minimizing side effects, would be of great interest. Studies have documented an inverse relationship between the incidence of hormone receptor negative breast cancer and adherence to a Mediterranean Diet, particularly higher consumption of fish and olive oil. Here, we performed a review of studies over the last 5 years investigating the effects of fish oil, olive oil and their components in model systems of TNBC. We included studies that focused on the fish oil ω-3 essential fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) in addition to olive oil polyphenolic compounds and oleic acid. Both beneficial and deleterious effects on TNBC model systems are reviewed and we highlight how multiple components of these Mediterranean Diet oils target signaling pathways known to be aberrant in TNBC including PI3K/Akt/mTOR, NF-κB/COX2 and Wnt/β-catenin.

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A novel patient-derived xenograft model for claudin-low triple-negative breast cancer

Abstract: Here, we characterize a claudin-low TNBC patient-derived xenograft model that can be utilized for therapeutic research studies.

Cited by 23 publications

References 42 publications

Panobinostat suppresses the mesenchymal phenotype in a novel claudin-low triple negative patient-derived breast cancer model

Panobinostat suppresses the mesenchymal phenotype in a novel claudin-low triple negative patient-derived breast cancer model

Breast Cancer Reconstruction: Design Criteria for a Humanized Microphysiological System

Do Olive and Fish Oils of the Mediterranean Diet Have a Role in Triple Negative Breast Cancer Prevention and Therapy? An Exploration of Evidence in Cells and Animal Models

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