UCLA researchers recently revealed a cell of origin for human prostate cancer. This analysis may offer improved predictive and diagnostic tools and development of advanced treatment measures for the disease.
Researchers highlighted that basal cells present in benign prostate tissue apparently become human prostate cancer in mice with weak immune systems. Previous analysis discovered that luminal cells in the prostate appeared to be the main cause for prostate cancer, revealing that malignancies closely resembled luminal cells.
“Certainly, the dominant thought is that human prostate cancer arose from the luminal cells because the cancers had more features resembling luminal cells. But we were able to start with a basal cell and induce human prostate cancer, and now, as we go forward, this gives us a place to look in understanding the sequence of genetic events that initiates prostate cancer and defining the cell-signaling pathways that may be at work fueling the malignancy, helping us to potentially uncover new targets for therapy,” commented Witte, senior author of the study and a Howard Hughes Medical Institute Investigator.
Researchers collected healthy tissues from prostate biopsies and classified the cells into groups of luminal cells and groups of basal cells depending on the surface-marker expression. The analysis has shed light on certain modified genes known to cause cancer into both cell populations with the help of viral vectors. Investigators further placed these cells in mice to evaluate which cell developed cancer.
Andrew Goldstein, a UCLA graduate student and first author of the study, shared, “Because of the widespread belief that luminal cells were the root of human prostate cancer, it would have been those cells examined and targeted to treat the disease. This study tells us that basal cells play an important role in the prostate cancer development process and should be an additional focus of targeted therapies.”
Researchers identified that normal prostate tissue known as basal cells have a more stem like function, highlighting that they multiply more to re-grow human prostate tissue. Luminal cells do not proliferate, however, produce essential proteins for production. Researchers are expected to carefully analyze basal cells in order to identify mechanisms that result in malignancy.
Goldstein quoted, “There are very few examples of taking benign cells and turning them into cancer experimentally. We usually study cancer cell lines created from malignant tumors. This study resulted in the creation of a novel model system that is highly adaptable, such that we can test any cellular pathway and its interactions with other genes known to induce cancer, and we can start with any type of cell, as long as it can be reproducibly purified.”
Limited knowledge on prostate cancer apparently makes it difficult to treat the disease in a specific way. Common targeted therapy used for prostate cancer is aimed at the androgen receptor and is not always an efficient method. The new human-in-mouse model developed for analysis was created by collecting healthy human prostate tissue. These tissues may provoke cancer once it is placed in mice, instead of taking malignant tissue that is already cancerous and implanting it.
Researchers could use this model to examine the efficiency of the latest types of therapeutics. They can compare therapeutic effectiveness by using genetic events to activate specific signaling pathways. Deconstructing a specific tissue and then reconstructing it may also help understand how cells modify during the progression of cancer.
“We know those cells are malignant, but we don’t know how they got there. By starting with healthy cells and turning them into cancer, we can study the cancer development process. If we understand where the cancer comes from, we may be able to develop better predictive and diagnostic tools. If we had better predictive tools, we could look earlier in the process of cancer development and find markers that are better than the current PSA test at catching the disease early, when it is more treatable,” remarked Goldstein.
Augmenting PSA levels may highlight the presence of cancer forming in the prostate. Basal cells are reportedly one of the causes for human prostate cancer. However, researchers can evaluate pre-malignant basal cells and identify what they reveal, bringing the possibility of pinpointing a new marker for early detection. A therapy focused on pre-malignant basal cells, that are about to turn malignant, could provide a way to avoid cancer before it becomes hazardous.
These findings were presented on July 30, 2010 in the peer-reviewed journal Science.