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A vascularized breast cancer spheroid platform for the ranked evaluation of tumor microenvironment-targeted drugs by light sheet fluorescence microscopy

Author

Listed:
  • David Ascheid

    (Julius-Maximilians-Universität Würzburg)

  • Magdalena Baumann

    (Julius-Maximilians-Universität Würzburg)

  • Jürgen Pinnecker

    (Julius-Maximilians-Universität Würzburg)

  • Mike Friedrich

    (Julius-Maximilians-Universität Würzburg)

  • Daniel Szi-Marton

    (Julius-Maximilians-Universität Würzburg)

  • Cornelia Medved

    (Julius-Maximilians-Universität Würzburg)

  • Maja Bundalo

    (Universitätsklinikum Würzburg)

  • Vanessa Ortmann

    (Julius-Maximilians-Universität Würzburg)

  • Asli Öztürk

    (Julius-Maximilians-Universität Würzburg)

  • Rajender Nandigama

    (Julius-Maximilians-Universität Würzburg
    Max Planck Institute of Heart and Lung Research)

  • Katherina Hemmen

    (Julius-Maximilians-Universität Würzburg)

  • Süleymann Ergün

    (Julius-Maximilians-Universität Würzburg)

  • Alma Zernecke

    (Universitätsklinikum Würzburg)

  • Matthias Hirth

    (Technische Universität Illmenau)

  • Katrin G. Heinze

    (Julius-Maximilians-Universität Würzburg)

  • Erik Henke

    (Julius-Maximilians-Universität Würzburg
    Julius-Maximilians-Universität Würzburg)

Abstract

Targeting the supportive tumor microenvironment (TME) is an approach of high interest in cancer drug development. However, assessing TME-targeted drug candidates presents a unique set of challenges. We develop a comprehensive screening platform that allows monitoring, quantifying, and ranking drug-induced effects in self-organizing, vascularized tumor spheroids (VTSs). The confrontation of four human-derived cell populations makes it possible to recreate and study complex changes in TME composition and cell-cell interaction. The platform is modular and adaptable for tumor entity or genetic manipulation. Treatment effects are recorded by light sheet fluorescence microscopy and translated by an advanced image analysis routine in processable multi-parametric datasets. The system proved to be robust, with strong interassay reliability. We demonstrate the platform’s utility for evaluating TME-targeted antifibrotic and antiangiogenic drugs side-by-side. The platform’s output enabled the differential evaluation of even closely related drug candidates according to projected therapeutic needs.

Suggested Citation

  • David Ascheid & Magdalena Baumann & Jürgen Pinnecker & Mike Friedrich & Daniel Szi-Marton & Cornelia Medved & Maja Bundalo & Vanessa Ortmann & Asli Öztürk & Rajender Nandigama & Katherina Hemmen & Sül, 2024. "A vascularized breast cancer spheroid platform for the ranked evaluation of tumor microenvironment-targeted drugs by light sheet fluorescence microscopy," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48010-z
    DOI: 10.1038/s41467-024-48010-z
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    References listed on IDEAS

    as
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