Sensitivity of magnetic resonance elastography to extracellular matrix and cell motility in human prostate cancer cell line-derived xenograft models

Avan Kader; Joachim Snellings; Lisa C Adams; Pablo Gottheil; Dilyana B Mangarova; Jennifer L Heyl; Jan O Kaufmann; Jana Moeckel; Julia Brangsch; Timo A Auer; Federico Collettini; Frank Sauer; Bernd Hamm; Josef Käs; Ingolf Sack; Marcus R Makowski; Jürgen Braun

doi:10.1016/j.bioadv.2024.213884

Sensitivity of magnetic resonance elastography to extracellular matrix and cell motility in human prostate cancer cell line-derived xenograft models

Biomater Adv. 2024 Jul:161:213884. doi: 10.1016/j.bioadv.2024.213884. Epub 2024 Apr 29.

Authors

Avan Kader¹, Joachim Snellings², Lisa C Adams³, Pablo Gottheil⁴, Dilyana B Mangarova⁵, Jennifer L Heyl⁶, Jan O Kaufmann⁷, Jana Moeckel⁸, Julia Brangsch⁹, Timo A Auer¹⁰, Federico Collettini¹¹, Frank Sauer¹², Bernd Hamm¹³, Josef Käs¹⁴, Ingolf Sack¹⁵, Marcus R Makowski¹⁶, Jürgen Braun¹⁷

Affiliations

¹ Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany; Department of Biology, Chemistry and Pharmacy, Institute of Biology, Freie Universität Berlin, Königin-Luise-Str. 1-3, 14195 Berlin, Germany; Technical University of Munich, Department of Diagnostic and Interventional Radiology, Ismaninger Str. 22, 81675 Munich, Germany. Electronic address: [email protected].
² Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany. Electronic address: [email protected].
³ Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany; Technical University of Munich, Department of Diagnostic and Interventional Radiology, Ismaninger Str. 22, 81675 Munich, Germany. Electronic address: [email protected].
⁴ Peter Debye Institute for Soft Matter Physics, Leipzig University, Linnéstraße 5, 04103 Leipzig, Germany.
⁵ Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany. Electronic address: [email protected].
⁶ Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany. Electronic address: [email protected].
⁷ Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany; Bundesanstalt für Materialforschung und -prüfung (BAM), Division 1.5 Protein Analysis, Richard-Willstätter-Str. 11, 12489 Berlin, Germany. Electronic address: [email protected].
⁸ Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany. Electronic address: [email protected].
⁹ Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany; Technical University of Munich, Department of Diagnostic and Interventional Radiology, Ismaninger Str. 22, 81675 Munich, Germany. Electronic address: [email protected].
¹⁰ Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany; Berlin Insitute of Health (BIH), Berlin, Germany. Electronic address: [email protected].
¹¹ Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany; Berlin Insitute of Health (BIH), Berlin, Germany. Electronic address: [email protected].
¹² Peter Debye Institute for Soft Matter Physics, Leipzig University, Linnéstraße 5, 04103 Leipzig, Germany. Electronic address: [email protected].
¹³ Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany. Electronic address: [email protected].
¹⁴ Peter Debye Institute for Soft Matter Physics, Leipzig University, Linnéstraße 5, 04103 Leipzig, Germany. Electronic address: [email protected].
¹⁵ Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany. Electronic address: [email protected].
¹⁶ Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany; Technical University of Munich, Department of Diagnostic and Interventional Radiology, Ismaninger Str. 22, 81675 Munich, Germany; King's College London, School of Biomedical Engineering and Imaging Sciences, St Thomas' Hospital, Westminster Bridge Road, London SE1 7EH, United Kingdom. Electronic address: [email protected].
¹⁷ Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany. Electronic address: [email protected].

PMID: 38723432
DOI: 10.1016/j.bioadv.2024.213884

Abstract

Prostate cancer (PCa) is a significant health problem in the male population of the Western world. Magnetic resonance elastography (MRE), an emerging medical imaging technique sensitive to mechanical properties of biological tissues, detects PCa based on abnormally high stiffness and viscosity values. Yet, the origin of these changes in tissue properties and how they correlate with histopathological markers and tumor aggressiveness are largely unknown, hindering the use of tumor biomechanical properties for establishing a noninvasive PCa staging system. To infer the contributions of extracellular matrix (ECM) components and cell motility, we investigated fresh tissue specimens from two PCa xenograft mouse models, PC3 and LNCaP, using magnetic resonance elastography (MRE), diffusion-weighted imaging (DWI), quantitative histology, and nuclear shape analysis. Increased tumor stiffness and impaired water diffusion were observed to be associated with collagen and elastin accumulation and decreased cell motility. Overall, LNCaP, while more representative of clinical PCa than PC3, accumulated fewer ECM components, induced less restriction of water diffusion, and exhibited increased cell motility, resulting in overall softer and less viscous properties. Taken together, our results suggest that prostate tumor stiffness increases with ECM accumulation and cell adhesion - characteristics that influence critical biological processes of cancer development. MRE paired with DWI provides a powerful set of imaging markers that can potentially predict prostate tumor development from benign masses to aggressive malignancies in patients. STATEMENT OF SIGNIFICANCE: Xenograft models of human prostate tumor cell lines, allowing correlation of microstructure-sensitive biophysical imaging parameters with quantitative histological methods, can be investigated to identify hallmarks of cancer.

Keywords: Apparent diffusion coefficient; Collagen; Elastin; Fluidity; Magnetic resonance elastography; Nuclear shape; Prostate cancer; Quantitative histology; Stiffness.

MeSH terms

Animals
Cell Line, Tumor
Cell Movement*
Diffusion Magnetic Resonance Imaging / methods
Elasticity Imaging Techniques* / methods
Extracellular Matrix* / metabolism
Extracellular Matrix* / pathology
Humans
Male
Mice
Prostatic Neoplasms* / diagnostic imaging
Prostatic Neoplasms* / pathology