Studying Cell Signaling in the Prostate

While prostate cancer may not be as deadly as other cancers – five-year survival rates can exceed 90%, especially if the disease is localized – incidence rates overall are increasing. For 2019 alone, The American Cancer Society predicts the United States will see roughly 175,000 new cases and 32,000 deaths associated with prostate cancer.

As the prevalence of prostate cancer continues to grow, researchers are asking fundamental, but illuminating, questions about cell biology in the prostate. For example, how might signaling in niche cells – the clusters of cells that promote stem cells – affect how cells grow in different regions of the prostate?

Now, a new article published in the journal Cell Stem Cell details the findings of a study led by Dr. Li Xin, a Professor of Urology and a Faculty Member at the University of Washington Institute for Stem Cell and Regenerative Medicine (ISCRM), that could have implications for the future of prostate cancer research.

Specifically, the Dr. Xin and his research team at ISCRM were seeking answers to two key questions. What regulates the signaling that controls cell growth in the prostate? And why does the proliferation of cells seem to vary across different regions within the prostate?

“Previous studies have focused mostly on the role of Wnt signaling inside stem cells,” says Dr. Xin, referring a pathway by which proteins pass coded instructions onto cells. “We found that niche cells in the prostate not only generate Wnt ligands, but also possess Wnt signaling themselves.”

Using a mouse model, Dr. Xin and his team looked closely at stromal cells that produce Wnt ligands, which, in turn, activate Wnt signaling – a sort of on/off switch for the proliferation of progenitor cells in the prostate. In particular, the researchers were interested in one area of the prostate: the proximal prostatic duct, which is considered a prostate stem cell niche in mice.

Dr. Xin explains the primary findings. “We showed how the proliferation of prostatic epithelial stem/progenitor cells is coordinately regulated by both epithelial cell-autonomous and stromal-driven mechanisms, converging on Wnt signaling.”

What does this mean for human medicine and the future of prostate cancer research? The key, says Dr. Xin, is using this new information about Wnt signaling to further expand our understanding of cell biology in the prostate.  “We know that the strength of Wnt signaling changes in different regions of the prostate, which we believe may explain why prostate cancer mostly occurs in the peripheral zone, and why prostate cancer in transition zone is relatively indolent.”

By testing this hypothesis through further research, Dr. Xin hopes to eventually learn more about how the stromal Wnt signaling affects prostate cancer progression and how to manipulate stromal signaling to prevent the progression of cancer in the first place.

Acknowledgments

We thank the Cytometry and Cell Sorting Core at Baylor College of Medicine (NIH AI036211, CA125123, and RR024574) for technical support and Joel M. Sederstrom for expert assistance. W.X. and B.D were supported by National Natural Science Foundation of China (81572536 and 81672850). This work was supported by NIDDK (R01DK092202 and R01DK107436 to L.X.).

Author Contributions

Conceptualization, L.X. and X.W.; Investigation, X.W., L.Z., Z.Z., O.-J.K., R.D., and L.T.; Formal Analysis, X.W., L.X., L.Z., Z.Z., O.-J.K., Y.Z., and C.J.C.; Writing – Original Draft, L.X.; Writing – Review & Editing, L.X. with input from X.W. and C.J.C.; Resources, H.N., R.D., W.B., M.M.T., F.X., P.N., M.M.I., B.D., and W.X.; Funding Acquisition, L.X.; Supervision, L.X.