Role of Long-Chain Fatty Acyl-CoA Synthetase 4 (ACSL4) in Prostate Cancer Progression
Qinghu Ren, Max X Kong, Xinyu Wu, Fang-Ming Deng, Jonathan Melamed, Marie E Monaco, Peng Lee. New York University School of Medicine, New York, NY
Background: Previous studies have shown that fatty acid biosynthetic enzymes fatty acid synthase and acetyl Co-A carboxylase are highly expressed in a variety of tumors, including prostate cancer. However, their precise roles in defining the malignant phenotype remains unclear. The purpose of this study was to examine the role of lipid metabolic enzyme, long-chain fatty acyl-CoA synthetase 4 (ACSL4), in prostate cancer.
Design: Immunohistochemistry was performed using ASCL4 antibody (LifeSpan BioSciences) in Formalin-Fixed and Paraffin-Embedded TMA with prostate cancers (n=155) and benign prostate tissue (n=124). Intensity levels, 0 (negative) to 3 (strong), and percentage score, 0 (0%) to 5 (100%), were recorded, resulting in a combined score for statistical analysis with an unpaired t-test. Lentiviral-ACSL4 constructs were transfected into LNCaP cells via Lipofectamine-mediated transfection. Cell proliferation was measured by WST assay and flow cytometry. Invasion assays were performed using BD Matrigel invasion chamber.
Results: Cytoplasmic staining of ASCL4 is observed in both benign prostate tissue and prostate cancers. The mean expression of cytoplasmic ASCL4 is increased in prostate cancers as compared to benign (1.3 folds, p<0.0001). Among all prostate cancer patients, African Americans shows significantly higher expression of ASCL4 compared to Caucasians (p<0.05). Higher stage cancers show significantly increased percentage of ASCL4 expression (p<0.05). Increased ASCL4 expression (intensity only) is also observed in prostate cancer with positive margins (p<0.05) and in hormone resistant cancers (p<0.05). Consistently, overexpression of ACSL4 promotes proliferation in ACSL4-negative LNCaP cells in hormone-free media, and media with androgen or estrogen. In ACSL4 stably transfected LNCaP cells, there was an increase in the number of cells invading through the collagen-based Matrigel. However, the invasion capability was diminished when ACSL4-positive PC3 cells were treated with ACSL4 siRNA.
Conclusions: A significant up-regulation of cytoplasmic ASCL4 expression is observed in prostate cancer both in vivo and in vitro, which correlates with prostate cancer types with poor clinical prognosis (higher stage, margin positive and hormone resistant), suggesting ASCL4 may play a role in cancer progression.
Category: Genitourinary (including renal tumors)
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 152, Monday Morning