Abstract | March 15, 2024

Metastatic Prostate Cancer Cells Effect on Tumor Microenvironment

Jordan Beam, Bachelor of Science in Biomedical Sciences, Medical Student, 2nd Year, Heersink School of Medicine, Birmingham, AL

Renee Ormsby, PhD, University of Oxford, Oxford U.K.; Young Eun Park, PhD, University of Oxford, Oxford U.K.; Claire Edwards, PhD University of Oxford, Oxford U.K.; Jessica Whitburn, PhD University of Oxford, Oxford U.K.; Majd Zayzafoon, M.D. PhD University of Alabama at Birmingham Heersink School of Medicine, Birmingham, AL

Learning Objectives

  1. Have a better understanding of the tumor microenvironment, metastatic prostate cancer cell's interaction with osteoblasts and adipocytes, and be able to describe future targets for pharmocologic prostate cancer therapy

Background: Bone is the main site of prostate cancer (PCa) metastasis, with an increased mortality rate for PCa patients. PCa cells interact with osteoblasts (bone-forming cells) to colonize the bone microenvironment (including adipocytes). The exact interactions that occur between osteoblasts, adipocytes and PCa cells are poorly understood. To investigate this, PCa cells were cultured ± osteoblasts or conditioned media from adipocytes.

Methods/Results: PCa cells (PC3 and LNCaP) and osteogenic cells (HS5, HOB and MC3T3) were co-cultured in transwells for 4 days. Cell viability was measured using Alamar Blue. PC3 cancer cells significantly reduced MC3T3 viability (3% decrease in 4 days). RNA was collected from PC3 and MC3T3 co-culture to determine changes in gene expression of G6PD (pentose phosphate metabolic pathway enzyme suggesting PCa growth and migration) OCN and COL1A1. In MC3T3 cells co-cultured with PC3, an increase in osteoblast markers-OCN, COL1A1, and RANKL-was detected suggesting interaction with PC3 cells induces MC3T3 differentiation. MC3T3 cells were cultured with conditioned media from PC3 cells. Bright-field microscopy showed MC3T3 cells rounding/clumping before undergoing apoptosis. Live/Dead staining of MC3T3 + PC3 conditioned media at 48 hrs displayed a similar morphology suggesting that prostate cancer cells interacting with MC3T3 cells could induce their apoptosis. PC3 cells were also cultured with conditioned media from ST2 differentiated adipocytes, inducing a marginal increase in PC3 viability (210% increase).

Conclusions: This work demonstrates that osteoblasts and adipocytes likely play key roles in PCa bone metastasis, with cancer-bone crosstalk impacting cell growth and differentiation.

References and Resources

  1. Whitburn J, Rao SR, Morris EV, Tabata S, Hirayama A, Soga T, Edwards JR, Kaya Z, Palmer C, Hamdy FC, Edwards CM. Metabolic profiling of prostate cancer in skeletal microenvironments identifies G6PD as a key mediator of growth and survival. Sci Adv. 2022 Feb 25;8(8):eabf9096. doi: 10.1126/sciadv.abf9096. Epub 2022 Feb 25. PMID: 35213227; PMCID:PMC8880772.
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