The development of humanised 3D bioprinted models of endocrine resistant breast cancer

Stephanie Agbana; Hunter Mangelberg; Salma Ebrahim; Rachel Bleach; Massimiliano Garre; Lance Hudson; O; Arnold Hill; Marie McIlroy

doi:10.1530/endoabs.109.OC2.4

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Endocrine Abstracts (2025) 109 OC2.4 | DOI: 10.1530/endoabs.109.OC2.4

SFEBES2025 Oral Communications Endocrine Cancer and Late Effects (6 abstracts)

The development of humanised 3D bioprinted models of endocrine resistant breast cancer

Stephanie Agbana ^1,2 , Hunter Mangelberg ¹ , Salma Ebrahim ^1,3 , Rachel Bleach ^1,2 , Massimiliano Garre ⁴ , Lance Hudson ^2,5 , Michael W. O’Reilly ^1,6 , Arnold Hill ⁵ & Marie McIlroy ^1,2

Author affiliations

¹Androgens in Health & Disease Research Group, Department of Surgery, Royal College of Surgeons (RCSI), Dublin, Ireland; ²Endocrine Oncology Research Group, Department of Surgery, RCSI, Dublin, Ireland; ³Faculty of Science, The University of Amsterdam, Amsterdam, Netherlands; ⁴Super-Resolution Imaging Consortium, RCSI, Dublin, Ireland; ⁵Department of Surgery, Beaumont Hospital, Dublin, Ireland; ⁶Department of Endocrinology, University of Medicine and Health Sciences, RCSI, Dublin, Ireland

Introduction: Recent reports from our group, and others, have shown that an androgenic steroid environment is associated with poor response to therapy and facilitates anchorage-independent growth of breast cancer cells. Additionally, hormone receptor-positive breast cancer is challenging to study in vitro as they do not readily form organoids/ patient-derived xenografts (PDX) or fully recapitulate the tumour endocrine microenvironments. Using modern 3D bioprinting techniques and newly gained proficiencies in steroid detection, this study aims to define the utility of 3D bioprinting as a novel method in modelling androgens-mediated treatment resistance in breast cancer.

Methods: Using well-established breast cancer cell line models of endocrine resistance, we determine the influence of the steroid precursor androstenedione (A4) and other steroid ligands (E2, R1881, 11KT) in in vitro 2D and 3D-printed models.

Results: Various breast cancer cell lines retain cell viability post 3D bioprinting. Increased cell growth in response to androgens in 3D bioprinted cells compared to conventional 2D culturing highlights the efficiency of integrating the tumour steroid microenvironment into this model. Interestingly, androgens impacted the sensitivity of 3D bioprinted breast cancer cell lines to anti-AR therapies. Preliminary data suggest that primary breast tumours can be successfully disaggregated and bioprinted to generate 3D structures that resemble their respective in vivo histological phenotypes ex vivo. Patients’ tumour-associated conditioned medium derived from primary tumour-associated adipocytes were steroid profiled by LC-MS/MS, with results suggesting that individual tumour steroidogenesis impacts tumour growth and potentially facilitates endocrine resistance.

Conclusion: Integrating the tumour steroid microenvironment with 3D bioprinting might serve as a novel prognostic tool based on individual tumour steroid microenvironment. Successfully developing humanised models of breast cancers via 3D bioprinting would provide an alternative to existing ex vivo and in vivo models, potentially facilitating further research in uncovering the role of androgens in driving treatment resistance in breast cancer.