Current studies in the lab examine the role of the ATP-binding cassette (ABC) G2 cellular pump in prostate stem cell regulation in benign prostatic hyperplasia (BPH) growth. ABCG2 was originally discovered in a chemotherapy resistant breast cancer cell line, and is a member of a large family of ABC transporters that protect cells from a wide range of substrates. ABCG2 is proposed to protect cancer stem cells in many tumor types.
We have shown that ABCG2 mediated androgen efflux maintains prostate stem cells and that ABCG2 inhibition induces loss of stem cell properties. Thus, we propose that prostate stem cells in BPH and prostate cancer can be therapeutically targeted through ABCG2 inhibition. We are also performing targeted whole genome sequencing of cancer stem cells on single cells isolated via the Fluidigm system to determine stem cell heterogeneity. Targeting cancer stem cells is hypothesized to eliminate a potential source of primary cancer and recurrent prostate cancer, ultimately leading to reduction of primary cancer treatment and recurrent cancer.
Past and current funding include: RPCI Alliance Foundation, NYSTEM, Dr. Louis Sklarow Memorial Fund, and NIDDK.
Sabnis NG, Miller A, Titus MA, Huss WJ. The Efflux Transporter ABCG2 Maintains Prostate Stem Cells. Mol Cancer Res.2016 Nov 17. (Epub ahead of print)
Gangavarapu KJ, Miller A, Huss KJ. Gene Expression in Single Cells Isolated from the CWR-R1 Prostate Cancer Cell Line and Human Prostate Tissue Based on the Side Population Phenotype. Single Cell Biology. 2016, 5 (3).
Samant MD, Jackson CM, Felix CL, Jones AJ, Goodrich DW, Foster BA, and Huss WJ. Multi-Drug Resistance ABC Transporter Inhibition Enhances Murine Ventral Prostate Stem/Progenitor Cell Differentiation. Stem Cells and Development 2015, 24(10): 1236-1251.
Liao J, Qian F, Tchabo N, Mhawech-Fauceglia P, Beck A, Qian Z, Wang X, Huss WJ, Lele SB, Morrison CD, Odunsi K. Ovarian Cancer Spheroid Cells with Stem Cell-Like Properties Contribute to Tumor Generation, Metastasis and Chemotherapy Resistance Through Hypoxia-Resistant Metabolism. PLOS ONE 2014, 9(1): e84941
Gangavarapu KJ, Azabdaftari G, Morrison CD, Miller A, Foster BA, Huss WJ. Aldehyde Dehydrogenase and ATP Binding Cassette Transporter G2 (ABCG2) Functional Assays Isolate Different Populations of Prostate Stem Cells Where ABCG2 Function Selects for Cells with Increased Stem Cell Activity. Stem Cell Research and Therapy 2013; 4:132
Foster BA, Gangavarapu KJ, Mathew G, Azabdaftari G, Morrison CD, Miller A, Huss WJ. Human Prostate Side Population Cells Demonstrate Stem Cell Properties in Recombination with Urogenital Sinus Mesenchyme. PLOS ONE 2013; 8(1): e55062.
Huss WJ, Gray DR, Greenberg NM, Mohler JL, Smith, G.J. Breast Cancer Resistance Protein-Mediated Efflux of Androgen in Putative Benign and Malignant Prostate Stem Cells. Cancer Research 2005; 65: 6640-6650.