Cell Reports
Volume 37, Issue 7, 16 November 2021, 110027
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Combined whole-organ imaging at single-cell resolution and immunohistochemical analysis of prostate cancer and its liver and brain metastases

https://doi.org/10.1016/j.celrep.2021.110027Get rights and content
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Highlights

  • STP tomography has the resolution to detect tumor initiation and its progression in PC

  • Description of the micro-metastasis in mouse liver with whole-organ reconstruction

  • Whole-brain imaging and quantification of metastatic cells from primary prostate cancer

  • This technology allows the use of post hoc thick sections for traditional histology

Summary

Early steps of cancer initiation and metastasis, while critical for understanding disease mechanisms, are difficult to visualize and study. Here, we describe an approach to study the processes of initiation, progression, and metastasis of prostate cancer (PC) in a genetically engineered RapidCaP mouse model, which combines whole-organ imaging by serial two-photon tomography (STPT) and post hoc thick-section immunofluorescent (IF) analysis. STPT enables the detection of single tumor-initiating cells within the entire prostate, and consequent IF analysis reveals a transition from normal to transformed epithelial tissue and cell escape from the tumor focus. STPT imaging of the liver and brain reveal the distribution of multiple metastatic foci in the liver and an early-stage metastatic cell invasion in the brain. This imaging and data analysis pipeline can be readily applied to other mouse models of cancer, offering a highly versatile whole-organ platform to study in situ mechanisms of cancer initiation and progression.

Keywords

prostate cancer
serial two-photon tomography
whole-organ imaging
early metastasis
single-cell resolution

Data and code availability

  • All data reported in this paper will be shared by the lead contact upon request.

  • The codes were published in (Hyun et al., 2021; Kim et al., 2017) and are available upon request to Dr. Pavel Osten.

  • Any additional information required to reanalyze the data reported in this work paper is available from the lead contact upon request.

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Lead contact