Breast cancer organoids from a patient with giant papillary carcinoma as a high-fidelity model

Li, Xuelu; Pan, Bo; Song, Xiaoqing; Li, Ning; Zhao, Dongyi; Li, Man; Zhao, Zuowei

doi:10.1186/s12935-020-01171-5

Cited by 30 publications

(33 citation statements)

References 29 publications

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“…We found the single cell suspension methodology appealing when sorting, and the separation of a distinct cell population was of interest for the downstream analysis. However, organoids allowed us to preserve the original tumor architecture, which could heavily affect progression and drug resistance [92][93][94]. These results revealed a great opportunity for open collaborations, as biopsies can be frozen and preserved for future use in our studies, so we can receive samples from collaborators in order to perform custom screenings, and we have two successful techniques for material growth in the case of minimal initial tumor biopsy material.…”

Section: Discussionmentioning

confidence: 99%

Human Plasma-Derived 3D Cultures Model Breast Cancer Treatment Responses and Predict Clinically Effective Drug Treatment Concentrations

Calar

Plesselova

Bhattacharya

et al. 2020

Cancers

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Lack of efficacy and a low overall success rate of phase I-II clinical trials are the most common failures when it comes to advancing cancer treatment. Current drug sensitivity screenings present several challenges including differences in cell growth rates, the inconsistent use of drug metrics, and the lack of translatability. Here, we present a patient-derived 3D culture model to overcome these limitations in breast cancer (BCa). The human plasma-derived 3D culture model (HuP3D) utilizes patient plasma as the matrix, where BCa cell lines and primary BCa biopsies were grown and screened for drug treatments. Several drug metrics were evaluated from relative cell count and growth rate curves. Correlations between HuP3D metrics, established preclinical models, and clinical effective concentrations in patients were determined. HuP3D efficiently supported the growth and expansion of BCa cell lines and primary breast cancer tumors as both organoids and single cells. Significant and strong correlations between clinical effective concentrations in patients were found for eight out of ten metrics for HuP3D, while a very poor positive correlation and a moderate correlation was found for 2D models and other 3D models, respectively. HuP3D is a feasible and efficacious platform for supporting the growth and expansion of BCa, allowing high-throughput drug screening and predicting clinically effective therapies better than current preclinical models.

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Section: Discussionmentioning

confidence: 99%

Human Plasma-Derived 3D Cultures Model Breast Cancer Treatment Responses and Predict Clinically Effective Drug Treatment Concentrations

Calar

Plesselova

Bhattacharya

et al. 2020

Cancers

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“…The tumor sample was obtained from the MPD patient at the time of surgery. The BC tissue was treated as we had described before [ 16 ]. The study was conducted at The Second Hospital of Dalian Medical University (Dalian, China).…”

Section: Methodsmentioning

confidence: 99%

“…The tumor tissue was treated as we had described before [ 16 ]. The nipple tissue and tumor tissue was cut into pieces separately, washed with AdDF+++ (Advanced DMEM/F12 (Sigma, Saint Louis, MO, USA) containing 1× Glutamax (Invitrogen, Carlsbad, CA, USA), 10 mM HEPES (Invitrogen, Carlsbad, CA, USA) and 100 U/mL/100 mg/mL Penicillin/Streptomycin (Sigma, Saint Louis, MO, USA)) and digested in 3 mL medium [ 16 ] containing 1 mg/mL Collagenase (Sigma, Saint Louis, MO, USA) at 37 °C for appropriate time. The digested tissue was collected in 3 mL AdDF+++.…”

Section: Methodsmentioning

confidence: 99%

“…After gelation was completed, it was overlaid with 450 μL medium. Passaging of organoids was performed as we had described before [ 16 ].…”

Section: Methodsmentioning

confidence: 99%

“…However, the tumor cells gradually underwent senescence after six or seven passages and could not expand as long as cancer cell lines. Afterwards, we successfully established a BC tissue-derived organoid of papillary carcinoma which had been continuously propagated for more than 6 months by using the organoid culture method [ 16 ]. It is important for us to study molecular pathogenesis and pathophysiology of uncommon pathological types BC as above.…”

Section: Introductionmentioning

confidence: 99%

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Establishment and characterization of breast cancer organoids from a patient with mammary Paget’s disease

et al. 2020

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Background Mammary Paget’s disease (MPD) is an uncommon cutaneous intraepithelial malignancy with ulceration of the nipple or areola. Its pathogenesis and genomic mutation remain largely unknown and no cell lines are established from primary tumors. Methods We collected surgical tumor specimens from a 65-year-old Chinese woman diagnosed with MPD and established patient-derived breast cancer (BC) organoids from MPD using organoid culture technology. Results We successfully propagated BC organoids from a patient with MPD for more than 6 months. The organoids were cultured for long-term expansion without any change in spherical organoid morphology. Besides, the spherical organoid morphology did not change when they underwent cryopreservation after resuscitation. The H&E staining and immunohistochemistry analyses showed the similar morphological and histological features of the organoids compared with their paired original BC tissues. The organoids retained positive expression of breast cancer biomarkers: estrogen receptor, progesterone receptor, antigen Ki-67 and negative expression of human epidermal growth factor receptor 2. We also showed that MPD organoids recapitulated the unique genomic landscape including copy number alterations, mutational load, mutational signatures and cancer gene mutations by whole genome sequencing. In situ senescence-associated acid beta galactosidase assay confirmed senescence phenomenon existed in the process of organoids culture and there was no significant difference in the proportion of senescent organoids after organoid passage and resuscitation. Conclusions Our results suggested that an effective platform for ex vivo BC organoids from MPD patients could be used to explore clinicopathological and genomic characteristics of these patients.

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Tumor organoids: synergistic applications, current challenges, and future prospects in cancer therapy

Kalyani

Liu

et al. 2021

Cancer Communications

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Patient-derived cancer cells (PDCs) and patient-derived xenografts (PDXs) are often used as tumor models, but have many shortcomings. PDCs not only lack diversity in terms of cell type, spatial organization, and microenvironment but also have adverse effects in stem cell cultures, whereas PDX are expensive with a low transplantation success rate and require a long culture time. In recent years, advances in three-dimensional (3D) organoid culture technology have led to the development of novel physiological systems that model the tissues of origin more precisely than traditional culture methods. Patient-derived cancer organoids bridge the conventional gaps in PDC and PDX models and closely reflect the pathophysiological features of natural tumorigenesis and metastasis, and have led to new patient-specific drug screening techniques, development of individualized treatment regimens, and discovery of prognostic biomarkers and mechanisms of resistance. Synergistic combinations of cancer organoids with other technologies, for example, organ-on-a-chip, 3D bio-printing, and CRISPR-Cas9-mediated homology-independent organoid transgenesis, and with

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Breast cancer organoids from a patient with giant papillary carcinoma as a high-fidelity model

Cited by 30 publications

References 29 publications

Human Plasma-Derived 3D Cultures Model Breast Cancer Treatment Responses and Predict Clinically Effective Drug Treatment Concentrations

Human Plasma-Derived 3D Cultures Model Breast Cancer Treatment Responses and Predict Clinically Effective Drug Treatment Concentrations

Establishment and characterization of breast cancer organoids from a patient with mammary Paget’s disease

Tumor organoids: synergistic applications, current challenges, and future prospects in cancer therapy

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