Lipid profiles of prostate cancer cells

Sorvina, Alexandra; Bader, Christie A.; Caporale, Chiara; Carter, Elizabeth A.; Johnson, I. R.; Parkinson-Lawrence, Emma J.; Simpson, Peter V.; Wright, Phillip J.; Stagni, Stefano; Lay, Peter A.; Massi, Massimiliano; Brooks, Douglas A.; Plush, Sally E.

doi:10.18632/oncotarget.26222

Cited by 36 publications

(43 citation statements)

References 45 publications

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“…Data demonstrating the significant enrichment of three lipid classes (namely, PC, PE, and SM) in hormone-sensitive cells in comparison to normal control cells is consistent with previous reports in plasma from PCa patients [ 33 , 43 , 44 ]. Elevated concentrations of SM in plasma were previously reported in patients with PCa in comparison to the control group [ 45 ].…”

Section: Discussionsupporting

confidence: 91%

Identification of lipidomic profiles associated with drug-resistant prostate cancer cells

et al. 2021

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Background The association of circulating lipids with clinical outcomes of drug-resistant castration-resistant prostate cancer (DR-CRPC) is not fully understood. While it is known that increases in select lipids correlate to decreased survival, neither the mechanisms mediating these alterations nor the correlation of resistance to drug treatments is well characterized. Methods This gap-in-knowledge was addressed using in vitro models of non-cancerous, hormone-sensitive, CRPC and drug-resistant cell lines combined with quantitative LC-ESI-Orbitrap-MS (LC-ESI-MS/MS) lipidomic analysis and subsequent analysis such as Metaboanalyst and Lipid Pathway Enrichment Analysis (LIPEA). Results Several lipid regulatory pathways were identified that are associated with Docetaxel resistance in prostate cancer (PCa). These included those controlling glycerophospholipid metabolism, sphingolipid signaling and ferroptosis. In total, 7460 features were identified as being dysregulated between the cell lines studied, and 21 lipid species were significantly altered in drug-resistant cell lines as compared to nonresistant cell lines. Docetaxel resistance cells (PC3-Rx and DU145-DR) had higher levels of phosphatidylcholine (PC), oxidized lipid species, phosphatidylethanolamine (PE), and sphingomyelin (SM) as compared to parent control cells (PC-3 and DU-145). Alterations were also identified in the levels of phosphatidic acid (PA) and diacylglyceride (DAG), whose levels are regulated by Lipin (LPIN), a phosphatidic acid phosphatase that converts PA to DAG. Data derived from cBioPortal demonstrated a population of PCa patients expressing mutations aligning with amplification of LPIN1, LPIN2 and LPIN3 genes. Lipin amplification in these genes correlated to decreased survival in these patients. Lipin-1 mRNA expression also showed a similar trend in PCa patient data. Lipin-1, but not Lipin-2 or − 3, was detected in several prostate cancer cells, and was increased in 22RV1 and PC-3 cell lines. The increased expression of Lipin-1 in these cells correlated with the level of PA. Conclusion These data identify lipids whose levels may correlate to Docetaxel sensitivity and progression of PCa. The data also suggest a correlation between the expression of Lipin-1 in cells and patients with regards to prostate cancer cell aggressiveness and patient survivability. Ultimately, these data may be useful for identifying markers of lethal and/or metastatic prostate cancer.

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Section: Discussionsupporting

confidence: 91%

Identification of lipidomic profiles associated with drug-resistant prostate cancer cells

et al. 2021

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“…Data demonstrating the significant enrichment of four lipid classes (namely, PC, PE SM, Cer) in hormone-sensitive cells in comparison to normal control cells is consistent with previous reports in plasma from prostate cancer patients [29,43,44]. Elevated concentrations of SM in plasma were previously reported in patients with PCa in comparison to the control group [45].…”

Section: Discussionsupporting

confidence: 91%

“…The elevation of PE in prostate cancer cells agrees with the findings of increased in PE in patient plasma samples [43,56], as well as in prostate cancer cells (LNCaP, 22RV1 and DU-145), as compared to PNT2 cells [44]. PE has also been detected in high abundance in exosomes derived from PC-3 cells [57].…”

Section: Discussionsupporting

confidence: 86%

“…These data, as well as previous studies demonstrates that there are fundamental differences between the lipidome of non-cancer and cancer cells [44,[59][60][61]. Non-cancer cells typically exhibit neutral total membrane charge due to the presence of zwitterionic phospholipids (PC and SM) on the outer leaflet of the membrane and PS and PE located in the inner leaflet of the membrane [62][63][64].…”

Section: Discussionsupporting

confidence: 83%

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Identification of Lipidomic Profiles Associated with Drug-Resistant Prostate Cancer Cells

Ingram

Mansoura

Chou³

et al. 2020

Preprint

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BackgroundThe association of circulating lipids with clinical outcomes of drug-resistant castration-resistant prostate cancer (CRPC) is not fully understood. While it is known that increases in select lipids correlates to decreased survival, neither the mechanisms mediating these alterations nor the correlation of resistance to drug treatments are well characterized.MethodsWe addressed this gap-in-knowledge using in vitro models of non-cancerous, hormone-sensitive, CRPC and drug-resistant cell lines combined with quantitative LC-ESI-Orbitrap-MS lipidomic analysis and subsequent analysis such as Metaboanalyst and Lipid Pathway Enrichment (LIPEA).ResultsThis approach identified several lipid regulatory pathways associated with Docetaxel resistance in PCa. These included those controlling glycerophospholipid metabolism, sphingolipid signaling pathways and ferroptosis. In total, 7,460 features were identified as being dysregulated between the cell lines studied, and 21 lipid species were significantly altered in drug-resistant cell lines as compared to nonresistant cell lines. Docetaxel resistance cells (PC3-Rx and DU145-DR) and had higher levels of phosphatidylcholine (PC), oxidized lipid species, phosphatidylethanolamine (PE), and sphingomyelin (SM) as compared to parent control cells (PC-3 and DU-145). These cells also had higher levels of ceramides release into the media.ConclusionThese data identify lipids whose levels may correlate to Docetaxel sensitivity and progression of prostate cancer.

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“…Moreover, lipid metabolism is a highly androgen-sensitive process in prostate cancer cells (7) and lipid composition may therefore be a unique cellular readout of both androgen targeting and tumorigenesis. While panels of circulating plasma lipids have previously been associated with prostate cancer risk (8), diagnosis (9) and patient outcome (10), analysis of the prostate tumor lipidome has largely been confined to cell line-based studies (11)(12)(13), which lack clinical relevance. The recent evidence of malignancy-related changes in lipid composition of prostate tumors provided by mass spectrometry-based imaging studies (14)(15)(16)(17) supports undertaking a more detailed and quantitative study of the clinical prostate cancer lipidome.…”

Section: Introductionmentioning

confidence: 99%

Lipidomic profiling of clinical prostate cancer reveals targetable alterations in membrane lipid composition

Butler

Mah

Machiels

et al. 2020

Preprint

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Dysregulated lipid metabolism is a prominent feature of prostate cancer that is driven by androgen receptor (AR) signaling. Herein, we used quantitative mass spectrometry to define the "lipidome" in prostate tumors with matched benign tissues (n=21), independent tissues (n=47), and primary prostate explants cultured with a clinical AR antagonist, enzalutamide (n=43). Significant differences in lipid composition were evident and spatially visualized in tumors compared to matched benign samples. Notably, tumors featured higher proportions of monounsaturated lipids overall and elongated fatty acid chains in phosphatidylinositol and phosphatidylserine lipids. Significant associations between lipid profile and malignancy were detected, and PL composition was characteristically altered in patient tissues that responded to AR inhibition. Importantly, targeting of tumor-related lipid features, via inhibition of acetyl CoA carboxylase 1, significantly reduced cellular proliferation in tissue explants (n=13). This first characterization of the prostate cancer lipidome in clinical tissues revealed enhanced fatty acid synthesis, elongation and desaturation as tumor-defining features, with potential for therapeutic targeting.

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Lipid profiles of prostate cancer cells

Cited by 36 publications

References 45 publications

Identification of lipidomic profiles associated with drug-resistant prostate cancer cells

Identification of lipidomic profiles associated with drug-resistant prostate cancer cells

Identification of Lipidomic Profiles Associated with Drug-Resistant Prostate Cancer Cells

Lipidomic profiling of clinical prostate cancer reveals targetable alterations in membrane lipid composition

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