BERKELEY, CA (UroToday.com) - In this article, we showed that tumor suppressor PTEN is incorporated into the cargo of exosomes shed from prostate cancer cells. Interestingly, we couldn’t detect PTEN in the cargo of exosomes derived from normal prostate epithelial cells. This phenomenon refers to a mechanism adopted by cancer cells to pass the tumor suppression activity by incorporating PTEN into exosomes and removing it outside the cell. As this mechanism is not detected in normal cells, blocking the incorporation of PTEN into exosomes may represent a new therapeutic strategy for prostate cancer. Decoding this mechanism may provide a new generation of targeted therapies with fewer side effects than the available ones, which affect both cancer and normal cells.
Interestingly, normal subjects (healthy men) do not express detectable levels of PTEN in their blood exosomes, unlike prostate cancer patients who express detectable levels of PTEN. This suggests that exosomal PTEN can be a good diagnostic biomarker for prostate cancer. In addition, the levels of PTEN may have prediction value for the potential of prostate tumor to metastasize.
Currently, we are working on intensive validation for exosomal PTEN as a biomarker for prostate cancer. As for prostate specific antigen (PSA), it is well documented that it lacks specificity and prediction value, and it is associated with a reasonable number of false positive or negative cases, and overtreatment for low-risk cases. The detection of PSA in exosomes from both normal subjects and prostate cancer patients refers to a new fraction of PSA that can affect the value of PSA. We speculate that incorporation of this fraction in some formula to assess PSA value may enhance the specificity and prediction value of the PSA test. Our preliminary work so far showed that PSA in exosomes is not related to the detected PSA using the traditional test. In other words, it is not increased or decreased with the increased or decreased level of PSA resulted from prostate cancer. Therefore, it can mask the slight increase in PSA resulted from early tumor causing a defect in PSA detection, in the early stages of the disease.
Currently we are validating our results with a larger number and more diverse population of patients, patients with benign prostate hypertrophy (BPH), prostatitis, and normal subjects. Microvesicles/exosomes represent the new and future source for biomarkers for prostate and other types of cancer. In addition, deep investigation for the role of microvesicles/exosomes in cancer will reveal new mechanisms used by cancer cells to modulate their microenvironment. This will provide a better understanding of the complexity of cancer and reveal new opportunities to target cancer cells.
Khalid Al-Nedawi, PhD as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
Department of Medicine
McMaster University and St. Joseph’s Healthcare
50 Charlton Street East
Hamilton, Ontario, Canada