Study Links Normal Stem Cells To Aggressive Prostate Cancer

A study that revealed new findings about prostate cells may point to future strategies for treating aggressive and therapy-resistant forms of prostate cancer.

The study proved that the prostate basal cell layer contains adult stem cells, which possess a unique gene expression profile resembling the deadliest form of prostate cancer. The research was led by The University of Texas, MD Anderson Cancer Center with findings published in the Feb. 29, 2016 online issue of Nature Communications.

 “It has become very controversial as to whether the human prostate contains adult stem cells or not and where they are located within the basal or luminal cell compartments,” said Dean G. Tang, M.D., Ph.D., professor of epigenetics and molecular carcinogenesis at MD Anderson. “Our study provided definitive evidence that the prostate basal cell layer harbors self-renewing adult stem cells that are enriched in stem-cell genes.”  

The researchers realized that to date, large-scale sequencing studies have relied on heterogeneous tissue samples as the material for DNA and RNA extraction. Because these samples typically contain both epithelial and non-epithelial cells, they obscure gene expression differences between basal and luminal cell lineages. This may result in lost insights into the cells of origin for different types of prostate cancer.

Accordingly, the researchers undertook a detailed transcriptome analysis of human benign prostate basal and luminal cells by deep RNA sequencing (RNA-seq). They presented the results of this work on February 29 in the journal Nature Communications, in an article entitled “Stem Cell and Neurogenic Gene-Expression Profiles Link Prostate Basal Cells to Aggressive Prostate Cancer.” Essentially, the researchers found that basal and luminal cells expressed genes differently and that some basal cells represented self-renewing adult stem cells.

“Strikingly, basal cells preferentially express gene categories associated with stem cells, neurogenesis and ribosomal RNA (rRNA) biogenesis,” the authors detailed. “Consistent with this profile, basal cells functionally exhibit intrinsic stem-like and neurogenic properties with enhanced rRNA transcription activity. Of clinical relevance, the basal cell gene-expression profile is enriched in advanced, anaplastic, castration-resistant and metastatic prostate cancers.”

These proneural genes seem to play important functions in conferring stem cell-like properties upon some basal cells, noted Dr. Tang. This finding is significant because a subset of prostate cancers (less than 5%) is highly aggressive and does not respond to current anti-prostate cancer treatments such as endocrine therapy.

“Surprisingly, these hard-to-treat cancers also express a gene signature that overlaps with our normal basal stem cell gene expression profile, suggesting that basal stem cells may represent the cell-of-origin for these prostate cancers,” explained Dr. Tang. “Of significance, the basal stem cell gene expression profile is also linked to endocrine therapy-resistant cancer, which is lethal to virtually all advanced prostate cancer patients.”

Dr. Tang’s team also found that basal stem cells are enriched in a genetic component that is partially regulated by MYC, offering hope that the deadliest of prostate cancers and therapy-resistant prostate cancers may have a new therapeutic option.

“Our studies,” Dr. Tang added, “establish that therapy that combines Pol-I and MYC inhibitors may be a potential new line of treatment for highly metastatic and endocrine therapy-resistant prostate cancer.”