Basal and luminal cells are the two major types of epithelial cells in the prostate. These two types of cells are mostly independently sustained in adults and both can serve as the cells of origin for prostate cancer. Recent studies using mouse models revealed that prostate cancer originated from basal epithelial cells are more invasive than those derived from luminal cells. Interestingly, initiation of this invasive type of prostate cancer is limited by a cellular process called basal-to-luminal differentiation. We showed recently that basal-to-luminal differentiation is enhanced in the context of prostatitis induced by infection from uropathogenic bacteria, suggesting that prostate stromal microenvironment substantially impinge on the differentiation program of prostate basal epithelial cells. In this application, we propose to use a combination of molecular biological and genetic approaches to uncover how the bacterial infection induced prostatitis affects prostate stromal cell transcriptome. We seek to identify prostate stromal cell-mediated signaling that plays critical roles in regulation of basal epithelial cell differentiation, and verify whether they serve as prognostic markers for aggressive prostate cancer.
Distinguishing indolent prostate cancers from aggressive ones remains a major clinical challenge for prostate cancer. Our study will lead to the finding of novel stromal cell-expressed prognostic markers for aggressive prostate cancer, which will substantially reduce disease-related mortality and medical care cost.
| Su, Q; Zhang, B; Zhang, L et al. (2017) Jagged1 upregulation in prostate epithelial cells promotes formation of reactive stroma in the Pten null mouse model for prostate cancer. Oncogene 36:618-627 |
| Kwon, Oh-Joon; Zhang, Li; Wang, Jianghua et al. (2016) Notch promotes tumor metastasis in a prostate-specific Pten-null mouse model. J Clin Invest 126:2626-41 |
