Abstract
As the most common cancer in men, prostate cancer is molecularly heterogeneous. Contributing to this heterogeneity are the poorly understood metabolic adaptations of the two main types of prostate cancer, i.e., adenocarcinoma and small cell neuroendocrine carcinoma (SCNC), the latter being more aggressive and lethal. Using transcriptomics, untargeted metabolomics and lipidomics profiling on LASCPC-01 (prostate SCNC) and LNCAP (prostate adenocarcinoma) cell lines, we found significant differences in the cellular phenotypes of the two cell lines. Gene set enrichment analysis on the transcriptomics data showed 62 gene sets were upregulated in LASCPC-01, while 112 gene sets were upregulated in LNCAP. ChemRICH analysis on metabolomics and lipidomics data revealed a total of 25 metabolite clusters were significantly different. LASCPC-01 exhibited a higher glycolytic activity and lower levels of triglycerides, while the LNCAP cell line showed increases in one-carbon metabolism as an exit route of glycolytic intermediates and a decrease in carnitine, a mitochondrial lipid transporter. Our findings pinpoint differences in prostate neuroendocrine carcinoma versus prostate adenocarcinoma that could lead to new therapeutic targets in each type.
Highlights
Prostate cancer is diagnosed in over 160,000 men annually in the United States, making it the most common cancer in men
With 7615 out of 16,225 transcripts, almost half of all detected genes were differentially expressed between LASCPC-01 and LNCAP cell lines
The expression levels of 3251 transcripts were higher in the LASCPC-01 cell line, while 4364 transcripts were higher in the LNCAP cell line
Summary
Prostate cancer is diagnosed in over 160,000 men annually in the United States, making it the most common cancer in men. Androgen receptor signaling is the primary driver of prostate cancer, and subsequently, medical castration with androgen deprivation therapy is the backbone of all treatments in men with metastatic prostate cancer [1,2]. Estrogens may play a role in the pathogenesis of prostate cancer [3]. Estrogen effects are mediated by estrogen receptor α (ERα) and β (ERβ). ERα acts as an oncogene, while ERβ plays an anti-oncogenic role [3]. Selective ER modulators such as tamoxifen and raloxifene induce apoptosis in the androgen-sensitive human prostate cancer cell line LNCAP, Metabolites 2019, 9, 82; doi:10.3390/metabo9050082 www.mdpi.com/journal/metabolites
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