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Intravital Microscopy to Study the Effect of Matrix Metalloproteinase Inhibition on Acute Myeloid Leukemia Cell Migration in the Bone Marrow

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Proteases and Cancer

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2747))

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Abstract

Hematopoiesis is the process through which all mature blood cells are formed and takes place in the bone marrow (BM). Acute myeloid leukemia (AML) is a blood cancer of the myeloid lineage. AML progression causes drastic remodeling of the BM microenvironment, making it no longer supportive of healthy hematopoiesis and leading to clinical cytopenia in patients. Understanding the mechanisms by which AML cells shape the BM to their benefit would lead to the development of new therapeutic strategies. While the role of extracellular matrix (ECM) in solid cancer has been extensively studied during decades, its role in the BM and in leukemia progression has only begun to be acknowledged. In this context, intravital microscopy (IVM) gives the unique insight of direct in vivo observation of AML cell behavior in their environment during disease progression and/or upon drug treatments. Here we describe our protocol for visualizing and analyzing MLL-AF9 AML cell dynamics upon systemic inhibition of matrix metalloproteinases (MMP), combining confocal and two-photon microscopy and focusing on cell migration.

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Acknowledgments

We thank the Imperial College London Central Biomedical Services and Crick Biological Research Facilities for their support and C. Ferchaud from Quantum Optics and Laser Science group, Blackett Laboratory, Imperial College London, for the technical drawings. This work was funded by the Wellcome Investigator Award to C.L.C. 212304/Z/18/Z and CRUK Programme Foundation award to CLC C36195/A26770. CRUK PhD studentship to S.G.A. C36195/A27830. F.T. work was supported by the Wellcome Investigator Award 212304/Z/18/Z and the CRUK Programme Foundation C36195/A26770.

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Authors and Affiliations

  1. Department of Life Sciences, Imperial College London, London, UK

    Floriane S. Tissot, Sara Gonzalez-Anton & Cristina Lo Celso

  2. The Francis Crick Institute, London, UK

    Floriane S. Tissot, Sara Gonzalez-Anton & Cristina Lo Celso

  3. Centre for Haematology, Department of Immunology and Inflammation, Imperial College London, London, UK

    Cristina Lo Celso

Authors
  1. Floriane S. Tissot
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  2. Sara Gonzalez-Anton
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  3. Cristina Lo Celso
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Corresponding author

Correspondence to Cristina Lo Celso .

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Editors and Affiliations

  1. Department of Biochemical Sciences, School of Biosciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, UK

    Salvatore Santamaria

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Tissot, F.S., Gonzalez-Anton, S., Lo Celso, C. (2024). Intravital Microscopy to Study the Effect of Matrix Metalloproteinase Inhibition on Acute Myeloid Leukemia Cell Migration in the Bone Marrow. In: Santamaria, S. (eds) Proteases and Cancer. Methods in Molecular Biology, vol 2747. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-3589-6_17

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  • DOI: https://doi.org/10.1007/978-1-0716-3589-6_17

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-3588-9

  • Online ISBN: 978-1-0716-3589-6

  • eBook Packages: Springer Protocols

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