Role of Lipids and Lipid Metabolism in Prostate Cancer Progression and the Tumor's Immune Environment

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2022 Sep 9

PMID 36077824

Authors

Aino Siltari

Heimo Syvala

Yan-Ru Lou

Yuan Gao

Teemu J Murtola

Affiliations

Soon will be listed here.

Abstract

Modulation of lipid metabolism during cancer development and progression is one of the hallmarks of cancer in solid tumors; its importance in prostate cancer (PCa) has been demonstrated in numerous studies. Lipid metabolism is known to interact with androgen receptor signaling, an established driver of PCa progression and castration resistance. Similarly, immune cell infiltration into prostate tissue has been linked with the development and progression of PCa as well as with disturbances in lipid metabolism. Immuno-oncological drugs inhibit immune checkpoints to activate immune cells' abilities to recognize and destroy cancer cells. These drugs have proved to be successful in treating some solid tumors, but in PCa their efficacy has been poor, with only a small minority of patients demonstrating a treatment response. In this review, we first describe the importance of lipid metabolism in PCa. Second, we collate current information on how modulation of lipid metabolism of cancer cells and the surrounding immune cells may impact the tumor's immune responses which, in part, may explain the unimpressive results of immune-oncological treatments in PCa.

Citing Articles

Unveiling Lipid Metabolic Shifts in Different Stages of Oral Submucous Fibrosis: A New Horizon in Predicting Malignant Transformation.

Chandra A, Keerthika R, Agarwal R, Rai A, Khairnar M Indian J Otolaryngol Head Neck Surg. 2025; 77(2):659-666.

PMID: 40070756 PMC: 11890815. DOI: 10.1007/s12070-024-05216-3.

Prostate cancer cells elevate glycolysis and G6PD in response to caffeic acid phenethyl ester-induced growth inhibition.

Lin T, Chen P, Lin C, Wang B, Kuo Y, Yeh C BMC Cancer. 2025; 25(1):95.

PMID: 39819475 PMC: 11737093. DOI: 10.1186/s12885-025-13477-6.

Combined Blockade of Lipid Uptake and Synthesis by CD36 Inhibitor and SCD1 siRNA Is Beneficial for the Treatment of Refractory Prostate Cancer.

Chen J, Yu X, Yang G, Chen X, Gong C, Han L Adv Sci (Weinh). 2024; 12(8):e2412244.

PMID: 39736148 PMC: 11848597. DOI: 10.1002/advs.202412244.

Altered amino and fatty acids metabolism in Sudanese prostate cancer patients: insights from metabolic analysis.

Ahmed D, Abdel-Shafy E, Mohammed E, Alnour H, Ismail A, Cacciatore S J Circ Biomark. 2024; 13:36-44.

PMID: 39697480 PMC: 11653783. DOI: 10.33393/jcb.2024.3146.

Analysis of transcriptomic data reveals the landscape of cholesterol metabolism in prostate cancer and impact of related signature on survival.

Sun J, An Y, Xu M, Ma S, Liu C, Xu J Discov Oncol. 2024; 15(1):777.

PMID: 39692951 PMC: 11656003. DOI: 10.1007/s12672-024-01658-x.

References

Han W, Gao S, Barrett D, Ahmed M, Han D, Macoska J . Reactivation of androgen receptor-regulated lipid biosynthesis drives the progression of castration-resistant prostate cancer. Oncogene. 2017; 37(6):710-721. PMC: 5805650. DOI: 10.1038/onc.2017.385. View

Lounis M, Peant B, Leclerc-Desaulniers K, Ganguli D, Daneault C, Ruiz M . Modulation of de Novo Lipogenesis Improves Response to Enzalutamide Treatment in Prostate Cancer. Cancers (Basel). 2020; 12(11). PMC: 7698241. DOI: 10.3390/cancers12113339. View

Zhang Q, Sun L, Yang Z, Zhang G, Huo R . Influence of adipocytokines in periprostatic adipose tissue on prostate cancer aggressiveness. Cytokine. 2016; 85:148-56. DOI: 10.1016/j.cyto.2016.06.019. View

Li D, Li Y . The interaction between ferroptosis and lipid metabolism in cancer. Signal Transduct Target Ther. 2020; 5(1):108. PMC: 7327075. DOI: 10.1038/s41392-020-00216-5. View

Roberts R, Bergstralh E, Bass S, Lieber M, Jacobsen S . Prostatitis as a risk factor for prostate cancer. Epidemiology. 2004; 15(1):93-9. DOI: 10.1097/01.ede.0000101022.38330.7c. View

Lin H, Yeung N, Hastings J, Croucher D, Huynh K, Meikle T . Relationship between Circulating Lipids and Cytokines in Metastatic Castration-Resistant Prostate Cancer. Cancers (Basel). 2021; 13(19). PMC: 8508038. DOI: 10.3390/cancers13194964. View

Duscharla D, Bhumireddy S, Lakshetti S, Pospisil H, Murthy P, Walther R . Prostate Cancer Associated Lipid Signatures in Serum Studied by ESI-Tandem Mass Spectrometryas Potential New Biomarkers. PLoS One. 2016; 11(3):e0150253. PMC: 4784901. DOI: 10.1371/journal.pone.0150253. View

Zadra G, Loda M . Metabolic Vulnerabilities of Prostate Cancer: Diagnostic and Therapeutic Opportunities. Cold Spring Harb Perspect Med. 2017; 8(10). PMC: 6169980. DOI: 10.1101/cshperspect.a030569. View

Ingram L, Finnerty M, Mansoura M, Chou C, Cummings B . Identification of lipidomic profiles associated with drug-resistant prostate cancer cells. Lipids Health Dis. 2021; 20(1):15. PMC: 7890620. DOI: 10.1186/s12944-021-01437-5. View

10.

Kauerova S, Bartuskova H, Muffova B, Janousek L, Fronek J, Petras M . Statins Directly Influence the Polarization of Adipose Tissue Macrophages: A Role in Chronic Inflammation. Biomedicines. 2021; 9(2). PMC: 7923086. DOI: 10.3390/biomedicines9020211. View

11.

Li X, Chen Y, Hu P, Huang W . Fatostatin displays high antitumor activity in prostate cancer by blocking SREBP-regulated metabolic pathways and androgen receptor signaling. Mol Cancer Ther. 2014; 13(4):855-66. PMC: 4084917. DOI: 10.1158/1535-7163.MCT-13-0797. View

12.

Murtola T, Syvala H, Pennanen P, Blauer M, Solakivi T, Ylikomi T . The importance of LDL and cholesterol metabolism for prostate epithelial cell growth. PLoS One. 2012; 7(6):e39445. PMC: 3384647. DOI: 10.1371/journal.pone.0039445. View

13.

Guth A, Monk E, Agarwal R, Bergman B, Zemski-Berry K, Minic A . Targeting Fat Oxidation in Mouse Prostate Cancer Decreases Tumor Growth and Stimulates Anti-Cancer Immunity. Int J Mol Sci. 2020; 21(24). PMC: 7766808. DOI: 10.3390/ijms21249660. View

14.

Lim S, Wei J, Nguyen T, Shi H, Su W, Palacios G . Lipid signalling enforces functional specialization of T cells in tumours. Nature. 2021; 591(7849):306-311. PMC: 8168716. DOI: 10.1038/s41586-021-03235-6. View

15.

Kochuparambil S, Al-Husein B, Goc A, Soliman S, Somanath P . Anticancer efficacy of simvastatin on prostate cancer cells and tumor xenografts is associated with inhibition of Akt and reduced prostate-specific antigen expression. J Pharmacol Exp Ther. 2010; 336(2):496-505. DOI: 10.1124/jpet.110.174870. View

16.

Bramhecha Y, Guerard K, Audet-Walsh E, Rouzbeh S, Kassem O, Pernet E . Fatty acid oxidation enzyme Δ3, Δ2-enoyl-CoA isomerase 1 (ECI1) drives aggressive tumor phenotype and predicts poor clinical outcome in prostate cancer patients. Oncogene. 2022; 41(20):2798-2810. DOI: 10.1038/s41388-022-02276-z. View

17.

Masetti M, Carriero R, Portale F, Marelli G, Morina N, Pandini M . Lipid-loaded tumor-associated macrophages sustain tumor growth and invasiveness in prostate cancer. J Exp Med. 2021; 219(2). PMC: 8932635. DOI: 10.1084/jem.20210564. View

18.

Zhou X, Mao J, Ai J, Deng Y, Roth M, Pound C . Identification of plasma lipid biomarkers for prostate cancer by lipidomics and bioinformatics. PLoS One. 2012; 7(11):e48889. PMC: 3495963. DOI: 10.1371/journal.pone.0048889. View

19.

Lawler Jr J, Yin M, Diehl A, Roberts E, Chatterjee S . Tumor necrosis factor-alpha stimulates the maturation of sterol regulatory element binding protein-1 in human hepatocytes through the action of neutral sphingomyelinase. J Biol Chem. 1998; 273(9):5053-9. DOI: 10.1074/jbc.273.9.5053. View

20.

Shimano H . Sterol regulatory element-binding proteins (SREBPs): transcriptional regulators of lipid synthetic genes. Prog Lipid Res. 2001; 40(6):439-52. DOI: 10.1016/s0163-7827(01)00010-8. View