Engineering osteoblastic metastases to delineate the adaptive response of androgen-deprived prostate cancer in the bone metastatic microenvironment

Abstract

A three-dimensional model of prostate tumor cells growing in a bone-like microenvironment offers a new platform for studying how metastatic prostate cancers respond to therapies. Dietmar Hutmacher
and colleagues from the Queensland University of Technology in Brisbane, Australia, engineered a bone-like tissue environment by culturing bone progenitor cells in a fibrous polyester scaffold. The cells differentiated into bone-forming cells that produced the appropriate RNAs, proteins and minerals. The researchers then added various populations of prostate cancer cells to the constructs. Cell lines with the greatest bone metastatic potential grew best, and depriving cells of the hormone androgen led to a more aggressive disease phenotype consistent with that observed in the tumors of men with castration-resistant prostate cancer. The system offers a new way to test for relevant biomarkers and therapeutics in the laboratory.

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Funding

Department of Health | National Health and Medical Research Council (NHMRC)

Prostate Cancer Foundation of Australia (PCFA)

National Breast Cancer Foundation (NBCF)

Department of Education and Training | Australian Research Council (ARC)(IC160100026)

Advance Queensland Research Fellowship, QUT Vice Chancellor Research Fellowship

Movember Revolutionary Team Award