Using Human Stem Cells to Study the Role of the Stroma in the Initiation of Prostate Cancer

摘要

This project aimed to determine the role of tumor stroma in prostate cancer biology. To do this, we used a model of human embryonic stem cell (hESC) differentiation that was established in our laboratory. Using hESC-derived prostatic epithelial cells, we attempted to determine whether or not tumor stroma derived from human prostate cancer specimens induce and initiate carcinogenesis. The data generated in this funded project failed to support the hypothesis that prostatic tumour stroma was an initiator of tumorigenesis, but rather findings indicated that preceding events in the epithelial cells are most likely required to begin the process of malignancy. We went on to prove that CAF-induced malignancy was restricted to intermediate/transient amplifying (CD133-) cells, but not stem (CD133+) cells under the influence of stroma. This is an important finding, and provides new information regarding the initiation of prostate cancer, and the potential cancer cell of origin. Defining the role of prostatic tumour stroma in the initiation of carcinogenesis significantly impacts on the field of prostate cancer (and other major cancers). These findings, based on an innovative approach using human prostate stromal cells and embryonic stem cells, have provided fundamental advances to our understanding how cancer is initiated and thus may be prevented or treated. Our current data implicate both transient amplifying epithelial cells and stromal components of the tumor as therapeutic targets.