Researchers at Cold Spring Harbor Laboratory (CSHL) have developed a new way to study the life history of prostate cancer in mice. 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.

Their findings are published in the journal Cell Reports in a paper titled, “Combined whole-organ imaging at single-cell resolution and immunohistochemical analysis of prostate cancer and its liver and brain metastases.” The study was led by associate professor Pavel Osten, MD, PhD, professor Lloyd Trotman, PhD, and Julian Taranda, PhD, a former postdoc in the Osten lab.

“Early steps of cancer initiation and metastasis, while critical for understanding disease mechanisms, are difficult to visualize and study,” the researchers wrote. “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.”

The researchers’ approach uses a virus to transform one normal mouse prostate cell into a cancerous cell. The cancer cell can be located using a microscope technique called whole-organ serial two-photon tomography, which takes an image of all the cells on the top layer of an organ, slices off that piece, images what is in the next layer, and repeats the process until it has photographed the entire organ.

The researchers then used an artificial intelligence program, in which the machine created a 3D reconstruction of the organ, at single-cell resolution. Osten explained it is important because: “In the later stages of cancer, you have a big bulk of cancer cells and it’s easy to find them. In the early stage, you may have very few cells in the organ. And so looking with traditional methods is really painful because you have to slice and look and find.”

A 3D reconstruction of a mouse prostate 50 days after the start of cancer. The red mass represents the growing tumor, the green and purple represent prostate cells, and the blue represents DNA. Using a new method developed at CSHL, researchers can track the progression of prostate cancer from birth to its spread into other organs. In the image, the small red balls detached from the red mass are cancer cells that are beginning to migrate.
[Julian Taranda/Osten lab/CSHL, 2021]
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.

Their findings and new approach may pave the way for new therapeutics and studies on treating prostate cancer.