Among men, prostate cancer is the most commonly diagnosed cancer and the second leading cause of cancer-related deaths. Since the disease is clinically identified only when large tumors comprising hundreds of millions of cancer cells are present, studies in animal models applying sensitive whole-organ imaging and tissue analysis methods are needed to understand prostate cancer initiation and early progression, including early metastatic spread to distant tissues.
Cold Spring Harbor Laboratory (CSHL) Associate Professor Pavel Osten and Professor Lloyd Trotman have developed a new way to study the life history of prostate cancer in mice. The pair combined their expertise in whole-organ imaging and prostate cancer to track how prostate cancer cells grow into tumors and spread to other organs. Their method allows scientists to study the behavior and properties of prostate cancer, for the first time, in a setting that accurately mimics the disease in real life. The study was published in Cell Reports
The authors described a novel approach to the study of cancer in animal models, one that combines single-cell resolution imaging of entire organs by STPT, computational quantification of putative cancer cell distribution across the imaged organs, and immunostaining of thick tissue sections generated during STPT imaging to validate and further characterize the combination of molecular and morphological pathology. They demonstrated these methods in the study of prostate cancer in a fluorescent version of the RapidCaP model, a genetically engineered mouse (GEM) model for native metastatic prostate cancer, which is based on a focal deletion of Pten and Trp53 genes by lentivirus-based delivery of Cre recombinase directly into the prostate gland.
The STPT-based approach to imaging the different stages of prostate cancer in the RapidCaP model uniquely combines automated high-resolution whole-organ imaging and analysis of prostate cancer initiation, progression, and metastasis at cellular resolution with traditional IF analysis of cytoskeletal protein markers to further examine cellular features of prostate cancer cells in the prostate and other metastatic tissues.
The researchers were able to track the progression of prostate cancer cells from their birth up to 20 days later, when they started spreading within the organ. Later, these fugitive cells started migrating to the liver and, unexpectedly, the brain.
The scientists hope this versatile new method will help tackle unexplored questions about the early steps of cancer’s growth and escape into other organs, wherever it starts.
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. Combined whole-organ imaging at single-cell resolution and immunohistochemical analysis of prostate cancer and its liver and brain metastases. Cell Reports, 2021; 37 (7): 110027 DOI: 10.1016/j.celrep.2021.110027Go To Cell Reports