Skip to main content

Advertisement

Log in

Oxidized low-density lipoprotein is associated with advanced-stage prostate cancer

  • Research Article
  • Published:
Tumor Biology

Abstract

Clinical and epidemiological data suggest coronary artery disease shares etiology with prostate cancer (PCa). The aim of this work was to assess the effects of several serum markers reported in cardiovascular disease on PCa. Serum markers (oxidized low-density lipoprotein [ox-LDL], apolipoprotein [apo] B100, and apoB48) in peripheral blood samples from 50 patients from Fudan University Shanghai Cancer Center (FUSCC) with localized or lymph node metastatic PCa were investigated in this study. Twenty-five samples from normal individuals were set as controls. We first conducted enzyme-linked immunosorbent assay analysis to select candidate markers that were significantly different between these patients and controls. Then, the clinical relevance between OLR1 (the ox-LDL receptor) expression and PCa was analyzed in The Cancer Genome Atlas (TCGA) cohort. We also investigated the function of ox-LDL in PCa cell lines in vitro. Phosphorylation protein chips were used to analyze cell signaling pathways in ox-LDL-treated PC-3 cells. The ox-LDL level was found to be significantly correlated with N stage of prostate cancer. OLR1 expression was correlated with lymph node metastasis in the TCGA cohort. In vitro, ox-LDL stimulated the proliferation, migration, and invasion of LNCaP and PC-3 in a dose-dependent manner. The results of phosphoprotein microarray illustrated that ox-LDL could influence multiple signaling pathways of PC-3. Activation of proliferation promoting signaling pathways (including β-catenin, cMyc, NF-κB, STAT1, STAT3) as well as apoptosis-associating signaling pathways (including p27, caspase-3) demonstrated that ox-LDL had complicated effects on prostate cancer. Increased serum ox-LDL level and OLR1 expression may indicate advanced-stage PCa and lymph node metastasis. Moreover, ox-LDL could stimulate PCa proliferation, migration, and invasion in vitro.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.

    Article  PubMed  Google Scholar 

  2. He J, Chen W. Chinese cancer registry annual report. Beijing: Military Medical Science Press; 2012.

    Google Scholar 

  3. Gutt R, Tonlaar N, Kunnavakkam R, Karrison T, Weichselbaum RR, Liauw SL. Statin use and risk of prostate cancer recurrence in men treated with radiation therapy. J Clin Oncol Off J Am Soc Clin Oncol. 2010;28:2653–9.

    Article  CAS  Google Scholar 

  4. Park HS, Schoenfeld JD, Mailhot RB, Shive M, Hartman RI, Ogembo R, et al. Statins and prostate cancer recurrence following radical prostatectomy or radiotherapy: a systematic review and meta-analysis. Ann Oncol Off J Eur Soc Med Oncol / ESMO. 2013;24:1427–34.

    Article  CAS  Google Scholar 

  5. Thomas 2nd JA, Gerber L, Banez LL, Moreira DM, Rittmaster RS, Andriole GL, et al. Prostate cancer risk in men with baseline history of coronary artery disease: results from the REDUCE study. Cancer Epidemiol Biomarkers Prev: Publ Am Assoc Cancer Res cosponsored by the American Society of Preventive Oncology. 2012;21:576–81.

    Article  CAS  Google Scholar 

  6. Li N, Hao M, Phalen RF, Hinds WC, Nel AE. Particulate air pollutants and asthma. A paradigm for the role of oxidative stress in PM-induced adverse health effects. Clin Immunol. 2003;109:250–65.

    Article  CAS  PubMed  Google Scholar 

  7. Araujo JA, Nel AE. Particulate matter and atherosclerosis: role of particle size, composition and oxidative stress. Particle Fibre Toxicol. 2009;6:24.

    Article  Google Scholar 

  8. Ghio AJ, Carraway MS, Madden MC. Composition of air pollution particles and oxidative stress in cells, tissues, and living systems. J Toxic Environ Health B, Crit Rev. 2012;15:1–21.

    Article  CAS  Google Scholar 

  9. Kumar B, Koul S, Khandrika L, Meacham RB, Koul HK. Oxidative stress is inherent in prostate cancer cells and is required for aggressive phenotype. Cancer Res. 2008;68:1777–85.

    Article  CAS  PubMed  Google Scholar 

  10. Nguyen HL, Zucker S, Zarrabi K, Kadam P, Schmidt C, Cao J. Oxidative stress and prostate cancer progression are elicited by membrane-type 1 matrix metalloproteinase. Mol Cancer Res: MCR. 2011;9:1305–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Paschos A, Pandya R, Duivenvoorden WC, Pinthus JH. Oxidative stress in prostate cancer: changing research concepts towards a novel paradigm for prevention and therapeutics. Prostate Cancer Prostatic Dis. 2013;16:217–25.

    Article  CAS  PubMed  Google Scholar 

  12. Lubrano V, Balzan S. LOX-1 and ROS, inseparable factors in the process of endothelial damage. Free Radic Res. 2014;1–19.

  13. D’Amico AV. Statin use and the risk of prostate-specific antigen recurrence after radiation therapy with or without hormone therapy for prostate cancer. J Clin Oncol Off J Am Soc Clin Oncol. 2010;28:2651–2.

    Article  Google Scholar 

  14. Shen Y, Yang T, Guo S, Li X, Chen L, Wang T, et al. Increased serum ox-LDL levels correlated with lung function, inflammation, and oxidative stress in COPD. Mediat Inflamm. 2013;2013:972347.

    Google Scholar 

  15. Lu J, Mitra S, Wang X, Khaidakov M, Mehta JL. Oxidative stress and lectin-like ox-LDL-receptor LOX-1 in atherogenesis and tumorigenesis. Antioxid Redox Signal. 2011;15:2301–33.

    Article  CAS  PubMed  Google Scholar 

  16. Jiang YZ, Yu KD, Zuo WJ, Peng WT, Shao ZM. GATA3 mutations define a unique subtype of luminal-like breast cancer with improved survival. Cancer. 2014;120:1329–37.

    Article  CAS  PubMed  Google Scholar 

  17. Ye L, Yao XD, Wan FN, Qu YY, Liu ZY, Shen XX, et al. MS4A8B promotes cell proliferation in prostate cancer. Prostate. 2014;74:911–22.

    Article  CAS  PubMed  Google Scholar 

  18. Eke I, Schneider L, Forster C, Zips D, Kunz-Schughart LA, Cordes N. EGFR/JIP-4/JNK2 signaling attenuates cetuximab-mediated radiosensitization of squamous cell carcinoma cells. Cancer Res. 2013;73:297–306.

    Article  CAS  PubMed  Google Scholar 

  19. Kalin TV, Wang IC, Ackerson TJ, Major ML, Detrisac CJ, Kalinichenko VV, et al. Increased levels of the FoxM1 transcription factor accelerate development and progression of prostate carcinomas in both TRAMP and LADY transgenic mice. Cancer Res. 2006;66:1712–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Saraon P, Musrap N, Cretu D, Karagiannis GS, Batruch I, Smith C, et al. Proteomic profiling of androgen-independent prostate cancer cell lines reveals a role for protein S during the development of high grade and castration-resistant prostate cancer. J Biol Chem. 2012;287:34019–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Muenchen HJ, Poncza PJ, Pienta KJ. Different docetaxel-induced apoptotic pathways are present in prostate cancer cell lines LNCaP and PC-3. Urology. 2001;57:366–70.

    Article  CAS  PubMed  Google Scholar 

  22. Khaidakov M, Mitra S, Kang BY, Wang X, Kadlubar S, Novelli G, et al. Oxidized LDL receptor 1 (OLR1) as a possible link between obesity, dyslipidemia and cancer. PLoS One. 2011;6:e20277.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Chen M, Kakutani M, Minami M, Kataoka H, Kume N, Narumiya S, et al. Increased expression of lectin-like oxidized low density lipoprotein receptor-1 in initial atherosclerotic lesions of Watanabe heritable hyperlipidemic rabbits. Arterioscler Thromb Vasc Biol. 2000;20:1107–15.

    Article  CAS  PubMed  Google Scholar 

  24. Muralidharan A, Smith MT. Pathobiology and management of prostate cancer-induced bone pain: recent insights and future treatments. Inflammopharmacology. 2013;21:339–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Syvaranta S, Alanne-Kinnunen M, Oorni K, Oksjoki R, Kupari M, Kovanen PT, et al. Potential pathological roles for oxidized low-density lipoprotein and scavenger receptors SR-AI, CD36, and LOX-1 in aortic valve stenosis. Atherosclerosis. 2014;235:398–407.

    Article  CAS  PubMed  Google Scholar 

  26. Shiota M, Yokomizo A, Takeuchi A, Imada K, Kiyoshima K, Inokuchi J, Tatsugami K, Naito S. The feature of metabolic syndrome is a risk factor for biochemical recurrence after radical prostatectomy. J Surg Oncol. 2014

  27. Khaidakov M, Mehta JL. Oxidized LDL triggers pro-oncogenic signaling in human breast mammary epithelial cells partly via stimulation of MiR-21. PLoS One. 2012;7:e46973.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Kodydkova J, Vavrova L, Stankova B, Macasek J, Krechler T, Zak A. Antioxidant status and oxidative stress markers in pancreatic cancer and chronic pancreatitis. Pancreas. 2013;42:614–21.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Dingwei Ye.

Additional information

Fangning Wan and Xiaojian Qin contributed equally to this work.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Table 1

(XLSX 21 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wan, F., Qin, X., Zhang, G. et al. Oxidized low-density lipoprotein is associated with advanced-stage prostate cancer. Tumor Biol. 36, 3573–3582 (2015). https://doi.org/10.1007/s13277-014-2994-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-014-2994-6

Keywords

Navigation