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Multiscale Label-Free Imaging of Fibrillar Collagen in the Tumor Microenvironment

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The Tumor Microenvironment

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2614))

Abstract

With recent advances in cancer therapeutics, there is a great need for improved imaging methods for characterizing cancer onset and progression in a quantitative and actionable way. Collagen, the most abundant extracellular matrix protein in the tumor microenvironment (and the body in general), plays a multifaceted role, both hindering and promoting cancer invasion and progression. Collagen deposition can defend the tumor with immunosuppressive effects, while aligned collagen fiber structures can enable tumor cell migration, aiding invasion and metastasis. Given the complex role of collagen fiber organization and topology, imaging has been a tool of choice to characterize these changes on multiple spatial scales, from the organ and tumor scale to cellular and subcellular level. Macroscale density already aids in the detection and diagnosis of solid cancers, but progress is being made to integrate finer microscale features into the process. Here we review imaging modalities ranging from optical methods of second harmonic generation (SHG), polarized light microscopy (PLM), and optical coherence tomography (OCT) to the medical imaging approaches of ultrasound and magnetic resonance imaging (MRI). These methods have enabled scientists and clinicians to better understand the impact collagen structure has on the tumor environment, at both the bulk scale (density) and microscale (fibrillar structure) levels. We focus on imaging methods with the potential to both examine the collagen structure in as natural a state as possible and still be clinically amenable, with an emphasis on label-free strategies, exploiting intrinsic optical properties of collagen fibers.

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Acknowledgments

We thank Dr. Jayne Squirrell, Dr. Ellen Dobson, and Sam Griffin for very useful comments and edits on the manuscript. We acknowledge funding from NIH grants# U54CA268069 and R01CA238191. Figure 1 was created using BioRender.com.

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Authors and Affiliations

  1. Center for Quantitative Cell Imaging, University of Wisconsin-Madison, Madison, WI, USA

    Michael S. Nelson, Yuming Liu, Helen M. Wilson, Bin Li & Kevin W. Eliceiri

  2. Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, USA

    Michael S. Nelson, Helen M. Wilson, Bin Li & Kevin W. Eliceiri

  3. Morgridge Institute for Research, Madison, WI, USA

    Bin Li, Jeremy D. Rogers & Kevin W. Eliceiri

  4. Department of Medical Physics, University of Wisconsin-Madison, Madison, WI, USA

    Ivan M. Rosado-Mendez, Walter F. Block & Kevin W. Eliceiri

  5. McPherson Eye Research Institute, University of Wisconsin-Madison, Madison, WI, USA

    Jeremy D. Rogers & Kevin W. Eliceiri

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  1. Michael S. Nelson
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  2. Yuming Liu
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  1. Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, QC, Canada

    Josie Ursini-Siegel

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Nelson, M.S. et al. (2023). Multiscale Label-Free Imaging of Fibrillar Collagen in the Tumor Microenvironment. In: Ursini-Siegel, J. (eds) The Tumor Microenvironment. Methods in Molecular Biology, vol 2614. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2914-7_13

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