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Organoid models derived from patients with malignant phyllodes tumor of the breast

  • Preclinical Study
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Purpose

Phyllodes tumor of the breast is a kind of rare neoplasm, which accounts for less than 1% of all breast tumors. Malignant phyllodes tumor (MPT) is the highest risk subtype of phyllodes tumor, and is characterized by the tendency of local recurrence and distant metastasis. The prediction of prognosis and the individual therapy for MPT is still challenging. It’s urgent to develop a new reliable in vitro preclinical model in order to understand this disease better and to explore appropriate anticancer drugs for individual patients.

Methods

Two surgically resected MPT specimens were processed for organoid establishment. MPT organoids were subsequently subjected to H&E staining, immunohistochemical analysis and drug screening, respectively.

Results

We successfully established two organoid lines from different patients with MPT. The MPT organoids can well retain the histological features and capture the marker expression in original tumor tissues, including p63, vimentin, Bcl-2, CD34, c-Kit, and Ki-67, even after a long-term culture. The dose titration tests of eight typical chemotherapeutic drugs (paclitaxel, docetaxel, vincristine, doxorubicin, cisplatin, gemcitabine, cyclophosphamide, ifosfamide) on the two MPT organoid lines showed patient-specific drug responses and varying IC50 values. Of all the drugs, doxorubicin and gemcitabine showed the best anti-tumor effect on the two organoid lines.

Conclusion

Organoids derived from MPT may be a novel preclinical model for testing personalized therapies for patients with MPT.

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Data availability

The original contributions presented in the study are included in the article. Further inquiries can be directed to the corresponding authors.

Consent to publish

All authors have seen and approved the manuscript and consent publication.

Abbreviations

EGF:

Epidermal growth factor

ER:

Estrogen receptor

FBS:

Fetal bovine serum

FGF-7:

Fibroblast growth factor 7

FGF-10:

Fibroblast growth factor 10

H&E:

Hematoxylin and eosin

HER2:

Human epidermal growth factor receptor-2

HRCT:

High resolution computed tomography

IC50 :

Half-maximal inhibitory concentration

IHC:

Immunohistochemical

MPT:

Malignant phyllodes tumor of the breast

MRI:

Magnetic resonance imaging

PDXs:

Patient-derived xenografts

PR:

Progesterone receptor

ROCK:

Rho-associated protein kinase

WHO:

World Health Organization

2D:

Two-dimensional

3D:

Three-dimensional

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Funding

This work was supported by the National Key R&D Program of China (2019YFA0906000), the Guangdong Basic and Applied Basic Research Foundation (2021A1515110618, 2022A1515011428), the Shenzhen Science and Technology Program (KCXFZ20211020163407011, JCYJ20210324105612034, JCYJ20220531094206014, GJHZ20180928115030292), the Shenzhen San-Ming Project (SZSM201612010), the Shenzhen Key Medical Discipline Construction Fund (SZXK017), and the Scientific Research Foundation of PEKING UNIVERSITY SHENZHEN HOSPITAL (KYQD2023251).

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Authors and Affiliations

  1. Affiliated Hospital of Weifang Medical University, School of Clinical Medicine, Weifang Medical University, Weifang, 261000, Shandong, China

    Xinyu Chu & Jinsong He

  2. Department of Breast and Thyroid Surgery, Peking University Shenzhen Hospital, Shenzhen, 518036, Guangdong, China

    Xinyu Chu, Ming Wu, Yang Fu, Xuewei Wang, Huan Wang, Yang Xiao, Dong Chen & Jinsong He

  3. Department of the Cancer Center, Fujian Medical University Union Hospital, Fuzhou, 350000, Fujian, China

    Jianbo Yang

  4. Department of Otolaryngology | The Immunotherapy Research Laboratory, University of Minnesota, Minneapolis, MN, 55421, USA

    Jianbo Yang

Authors
  1. Xinyu Chu
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  2. Ming Wu
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  3. Jianbo Yang
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  4. Yang Fu
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  5. Xuewei Wang
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  6. Huan Wang
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  7. Yang Xiao
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  8. Dong Chen
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  9. Jinsong He
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Contributions

XC, MW, DC, and JH conceived the study and designed experiments; XC, YF, XW, HW, YX, and JH recruited patients, performed operations, and collected and curated clinical annotation data; XC, MW, and DC performed the experiments; all authors were involved in data analysis and interpretation of the results; XC, DC, JY, and JH wrote the manuscript. All authors reviewed and gave final approval.

Corresponding authors

Correspondence to Dong Chen or Jinsong He.

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The authors have no relevant financial or non-financial interests to disclose.

Ethical approval

This study was approved by the Human Ethical Committee of Peking University Shenzhen Hospital (Approval No. 2019-062), and was carried out in accordance with the Declaration of Helsinki.

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Informed consent was obtained from all individual participants included in the study.

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Chu, X., Wu, M., Yang, J. et al. Organoid models derived from patients with malignant phyllodes tumor of the breast. Breast Cancer Res Treat 200, 193–201 (2023). https://doi.org/10.1007/s10549-023-06973-5

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