Combined whole-organ imaging at single-cell resolution and immunohistochemical analysis of prostate cancer and its liver and brain metastases
Julian Taranda,
Grinu Mathew,
Kaitlin Watrud,
Nour El-Amine,
Matthew F. Lee,
Corey Elowsky,
Anastasiia Bludova,
Sintia Escobar Avelar,
Dawid G. Nowak,
Tse-Luen Wee,
John E. Wilkinson,
Lloyd C. Trotman,
Pavel Osten
Affiliations
Julian Taranda
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; Neurology Clinic and National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg 69120, Germany
Grinu Mathew
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; The Eppley Institute for Research in Cancer and Allied Diseases, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68105, USA
Kaitlin Watrud
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA
Nour El-Amine
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA
Matthew F. Lee
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA
Corey Elowsky
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA
Anastasiia Bludova
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA
Sintia Escobar Avelar
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA
Dawid G. Nowak
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; Division of Hematology and Medical Oncology, Department of Medicine, Meyer Cancer Center, Weill Cornell Medicine, New York, NY 10065, USA
Tse-Luen Wee
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA
John E. Wilkinson
Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA
Lloyd C. Trotman
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; Corresponding author
Pavel Osten
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; Corresponding author
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.
