Invention:
In this study, researchers at the University of Arizona investigated an early cancer invasion event using a unique in vivo model. Muscle invasion was tested by the ability of prostate cancer cells to colonize the inferior surface of the respiratory diaphragm of male NGS mice, invade into and through to the superior surface. They isolated and compared the biological, cellular, and molecular characteristics of “Inferior” non-invasive tumor. “Muscle-resident” cells that invaded and now reside within the diaphragm muscle of “Superior” cells that have completely traversed the diaphragm muscle.
The results show that superior cells have gained the ability to reach a bone metastatic site, as detected by bioluminescence, PET/MRI, and history of the femur in 50% of animals as compared to no bone metastases in animals injected with Inferior cells. The Superior cells have a differential gene expression signature as compared to Inferior cells of 264 genes that was positively associated with metastatic prostate cancer in humans. Of significant interest is that muscle-resident tumor cells differentially expressed 84 genes compared to both the Inferior and Superior cancer cells, highlighting the unique environment of the active mouse muscle.
Background:
Human prostate cancer cell lines are particularly difficult to establish, and most existing cell lines do not exhibit features commonly seen in human prostate cancer. Most available models either grow only in vivo as xenografts or are androgen insensitive and fail to express prostate-specific antigen (PSA). The lack of functionally relevant model systems of advanced prostate cancer has limited prostate cancer research and therapy development. However, this technology focuses on the aggressive prostate tumors that invade through a smooth muscle pseudo capsule in a process called extracapsular extension (ECE), escaping organ confinement. The presence of ECE defines the pT3a category in the pathological staging of prostate adenocarcinoma and is associated with an increased risk of biochemical recurrence, distant metastasis, and cancer-specific mortality. Although muscle invasion is required for ECE and distant metastasis, the cellular phenotypes that dictate this behavior is not understood.
Applications:
- Prostate cancer treatment
Advantages:
- New treatment method
- Promising results
- Includes method for producing
