Metastatic Prostate Tumors Harbor Stem Cell-Like Gene Signatures

More aggressive prostate tumor phenotypes exhibit stem cell-like gene expression patterns, report researchers at the University of California, Los Angeles (UCLA).

Analyzing biopsy samples from patients with metastatic prostate cancer who participated in Stand Up To Cancer Initiative clinical trials, the team identified a 91-gene transcription signature for prostate epithelial populations of basal stem cells-and that signature was very similar to gene expression patters in the same patients’ metastatic prostate cancer tumors, the team reported in the Proceedings of the National Academy of Sciences.¹

Previous research has suggested that aggressive tumors in other cancer types have stem cell-like traits, said lead study author Bryan A. Smith, PhD, of the UCLA Department of Microbiology, Immunology, and Molecular Genetics.

“We now know this to be true for the most aggressive form of prostate cancer,” Dr. Smith told OncoTherapy Network.

The findings indicate that metastatic prostate cancer “shares a conserved transcriptional program with normal adult prostate basal stem cells,” the team reported.¹

Most of the genes found to be upregulated in metastatic tumor cells had not before been identified in prostate tumors, except for two genes: CXCL5 and APOD. Among histological prostate cancer subtypes, small cell neuroendocrine carcinoma (SCNC) phenotypes were more stem-like than metastatic adenocarcinoma or organ-confined adenocarcinoma, the team reported.

Targeting the gene pathways involved in that transcriptional program might offer new strategies for treating advanced prostate cancer in the future, the coauthors believe.

“Therapies that target the more aggressive and late-stage forms of the prostate cancer are urgently needed,” noted Dr. Smith. “Our data suggests that targeting those pathways [that are] important to normal human prostate stem cell functioning may be a possible avenue for treating advanced or SCNC prostate cancer.”

“It would be very interesting to see if metastases from certain cancers share specific stem-like gene networks or if there is a general stem-like transcriptional profile common to all metastasis,” Dr. Smith said.

The similarity in metastatic tumor and stem cell gene expression profiles could be due to “field effects” in biopsied tissues, Dr. Smith was quick to caution.

“Field effects occur when histologically normal tissue adjacent to cancerous tissue acquires many of the same genetic alterations seen in the malignant region,” he explained. “This means that to the eye, the tissue appears to be normal, but at the molecular level, it resembles the cancer. This is a concern because biopsies could appear to have normal prostate tissue when in actuality this tissue is likely to become cancerous. For our study, it was extremely difficult to determine if field effects were occurring or if we were getting cellular contamination. Since this was the first study to compare these cell populations from human benign and cancer tissue, we didn’t have any other studies to compare our gene expression data to in order to determine if we had cellular contamination or a field effect.”

“Pinpointing the cellular traits of cancer - what makes those cells grow and spread - is crucial because then we can possibly target those traits to reverse or stop cancer’s progression,” said senior study author Owen Witte, MD, founding director of the UCLA Broad Stem Cell Research Center, in a press release. “Our findings will inform our work as we strive to find treatments for aggressive prostate cancer.”²

“I believe this research gives us important insight into the cellular nature of aggressive prostate cancer,” Dr. Witte said.

“There is still a lot of work that needs to be done before this new paradigm for prostate cancer treatment is translated to the clinic,” Dr. Smith said. “We are currently doing functional studies targeting those pathways common between the prostate basal stem cell and prostate SCNC for the treatment of advanced disease.”

References:

• Smith BA, Sokolov A, Uzunangelov V, et al. (2015). A basal stem cell signature identifies aggressive prostate cancer phenotypes. Proceedings of the National Academy of Sciences of the United States of America, Oct 12. pii: 201518007.
• Vogt-James M. (2015).UCLA-led study shows deadly prostate cancer cells have stem cell qualities. UCLA Newsroom.