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MicroRNA suppresses prostate cancer stem cells and metastasis

n cells without CD44.

  • Prostate tumors in mice that also received miR-34a treatment were one third to half the average size of those in control group mice.

  • In CD44-positive prostate cancer cell lines, treatment with miR-34a resulted in greatly reduced tumor incidence. Most dramatically, in one cell line, tumor regeneration was blocked in all 10 treated animals, while tumors formed in all 10 animals treated with the control miRNAs.

  • Many characteristics of cancer stem cells formation of self-renewing cells, clonal growth capacity and formation of spheres were suppressed when miR-34a was overexpressed in prostate cancer cell lines.

  • Most significantly, intravenous treatment of tumor-bearing mice with synthetic miR-34a reduced tumor burden by half in one tumor type. It also steeply reduced lung metastases in another tumor type, resulting in increased animal survival.

  • Interestingly, the researchers observed a consistent, inverse relationship between miR-34a levels and CD44, the surface marker used to enrich prostate cancer stem cells. For example, the CD44 protein and CD44-expressing cancer cells were reduced in tumors treated with the microRNA. Tumors with miR-34a blocked had higher levels of CD44 protein and messenger RNA.

  • Finally, knocking down CD44 with a short hairpin RNA produced the same results as treating cells with miR-34a did reduced tumor development, tumor burden and metastases.

    "There are many companies developing microRNA-based drugs," Tang said. "Delivery of miRNAs is a challenge, but the field is moving fast through the preclinical stage."

    Scientists from Austin-based Mirna Therapeutics collaborated on the study. Mirna has eight microRNAs in preclinical development, including miR-34a.


  • Contact: Scott Merville
    University of Texas M. D. Anderson Cancer Center

    Page: 1 2

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