• Logo
  • SBMUJournals

Osteopontin And Angiogenic Factors As New Biomarkers Of Prostate Cancer

Tomasz Wisniewski, Agnieszka Zyromska, Roman Makarewicz, Ewa Zekanowska



Purpose: The novel biomarkers that would identify patients at risk for relapse and metastatic spread are needed. The aim of this study was the evaluation of serum levels of osteopontin (OPN) and tumor endogenous angiogenic factors such as vascular–endothelial growth factor (VEGF), vascular-endothelial growth factor receptor 2 (VEGF R2), endostatin, angiostatin and thrombospondin 1, in prostate cancer (PC) patients.

Material and Methods: Blood concentrations of the analyzed parameters were determined in 40 prostate cancer patients eligible for radiotherapy as well as in the control group consisted of 25 volunteers. Commercial ELISA kits were used for the analysis.

Results: Significantly higher levels of OPN (101.49 ng/mL vs 59.88 ng/mL; P<.001), endostatin (252.60 ng/mL vs. 223.55 ng/mL; P=.043), angiostatin (47 ng/mL vs. 13 ng/mL; P=.047), VEGF (262.1 pg/mL vs. 138.0 pg/mL; P=.056) and VEGF R2 (11188.81 pg/mL vs. 9377.50 pg/mL; P=.047) were detected in PC patients compared with the control group. In PC patients we showed a positive correlation between OPN level and TNM clinical stage(R=0.36; P=.02) and negative correlation between OPN level and hemoglobin concentration (R=-0.33; P=.04).

Conclusion: The study showed higher levels of the angiogenic factors in PC patients compared with the control group and identified OPN as an indicator of the PC clinical stage as well as a decreased hemoglobin level.


Heidtmann HH, Nettelbeck DM, Mingels A, Jäger R, Welker HG, Kontermann RE. Generation of angiostatin-like fragments from plasminogen by prostate-specific antigen. Br J Cancer. 1999; 81: 1269–1273.

Denhardt DT, Noda M, O'Regan AW, Pavlin D, Berman JS. Osteopontin as a means to cope with envi-ronmental insults: regulation of inflammation, tissue remodeling, and cell survival. J Clin Invest. 2001; 107: 1055–1061.

Chakraborty G, Jain S, Behera R, et al. The multifaceted roles of osteopontin in cell signaling, tumor progression and angiogenesis. CurrMol Med. 2006; 6: 819–830.

Weber GF, Lett GS, Haubein NC: Meta-analysis of osteopontin as a clinical cancer marker. Oncol Rep. 2011; 25: 433-441.

Vordermark D, Said HM, Katzer A, et al. Plasma osteopontin levels in patients with head and neck cancer and cervix cancer are critically dependent on the choice of ELISA system. BMC Cancer. 2006; 6: 207.

Forootan SS, Foster CS, Aachi VR, et al. Prognostic significance of osteopontin expression in human prostate cancer. Int J Cancer. 2006; 118: 2255–2261.

Vergis R, Corbishley CM, Norman AR, et al. Intrinsic markers of tumour hypoxia and angiogenesis in localized prostate cancer and outcome of radical treatment: a retrospective analysis of two randomised radiotherapy trials and one surgical cohort study. Lancet Oncol. 2008; 9: 342-351.

Ramankulov A, Lein M, Kristiansen G, Loening SA, Jung K. Plasma osteopontin in comparison with bone markers as indicator of bone metastasis and survival outcome in patients with prostate cancer. Prostate 2007; 67: 330-340.

Thoms JW, Dal Pra A, Anborgh PH, et al. Plasma osteopontin as a biomarker of prostate cancer aggression: relationship to risk category and treatment response. Br J Cancer. 2012;107:840-846.

Snitcovsky I, Leitão GM, Pasini FS, et al. Plasma osteopontin levels in patients with head and neck cancer undergoing chemoradiotherapy. Arch Otolaryngol Head Neck Surg. 2009; 135: 807–811.

Hui EP, Sung FL, Yu BK, et al. Plasma osteopontin, hypoxia, and response to radiotherapy in nasopharyngeal cancer. Clin Cancer Res. 2008; 14: 7080–7087.

Ang C, Chambers AF, Tuck AB, Winquist E, Izawa JI. Plasma osteopontin levels are predictive of disease stage in patients with transitional cell carcinoma of the bladder. Br J Urol Int. 2005; 96: 803–805.

Nakamura KD, Tilli TM, Wanderley JL, et al. Osteopontin splice variants expression is involved on docetaxel resistance in PC3 prostate cancer cells. Tumour Biol. 2016; 37: 2655-2663.

Le QT, Sutphin PD, Raychaudhuri S, et al. Identification of osteopontin as a prognostic plasma marker for head and neck squamous cell carcinomas. Clin Cancer Res. 2003; 9: 59–67.

Nordsmark M, Eriksen JG, Gebski V, Alsner J, Horsman MR, Overgaard J. Differential risk assessments from five hypoxia specific assays: The basis for biologically adapted individualized radiotherapy in clinical head and neck cancer patients. Radiother Oncol. 2007; 83: 389–397.

Overgaard J, Eriksen JG, Nordsmark M, et al. Danish Head and Neck Cancer Study Group. Plasma osteopontin, hypoxia, and response to the hypoxia sensitiser nimorazole in radiotherapy of head and neck cancer: results from the DAHANCA 5 randomised double-blind placebo-controlled trial. Lancet Oncol. 2005; 6: 757–764.

Said HM, Hagemann C, Staab A, et al. Expression patterns of the hypoxia-related genes osteopontin, CA9, erythropoietin, VEGF and HIF-1alpha in human glioma in vitro and in vivo. Radiother Oncol. 2007; 83: 398–405.

Bache M, Reddemann R, Said HM, et al. Immunohistochemical detection of osteopontin in clinical head-and-neck cancer: prognostic role and correlation with oxygen electrode measurements, hypoxia-inducible-factor-1 –related markers and hemoglobin levels. Int J Radiat Oncol Biol Phys. 2006; 66: 1481–1487.

Riemann A, Ihling A, Reime S, Gekle M, Thews O. Impact of the Tumor Microenvironment on the Expression of Inflammatory Mediators in Cancer Cells. Adv Exp Med Biol. 2016; 923: 105-111.

Doll JA, Reiher FK, Crawford SE, Pins MR, Campbell SC, Bouck NP.. Thrombospondin-1, vascular endothelial growth factor and fibroblast growth factor-2 are key functional regulators of angiogenesis in the prostate. Prostate. 2001; 49: 293–305.

Duque JL, Loughlin KR, Adam RM, Kantoff PW, Zurakowski D, Freeman MR.. Plasma levels of vascular endothelial growth factor are increased in patients with metastatic prostate cancer. Urology. 1999; 54: 523–527.

Botelho F, Pina F, Lunet N. VEGF and prostate cancer: a systematic review. Eur J Cancer Prev. 2010; 19: 385–392.

Benzekry S,Gandolfi A, Hahnfeldt P. Global Dormancy of Metastases Due to Systemic Inhibition of Angiogenesis. PLoS One. 2014; 9: e84249.

Ferrer FA, Miller LJ, Lindquist R, et al. Expression of vascular endothelial growth factor receptors in human prostate cancer. Urology. 1999; 54: 567–572.

Perletti G, Concari P, Giardini R, et al. Antitumor activity of endostatin against carcinogen-induced rat primary mammary tumors. Cancer Res. 2000; 60: 1793–1796.

Hasle H, Clemmensen IH, Mikkelsen M. Risk of leukemia and solid tumors in individuals with Down’s syndrome. Lancet. 2000; 355: 165–169.

Lee JH, Isayeva T, Larson MR, et al. Endostatin: A novel inhibitor of androgen receptor function in prostate cancer. Proc Natl Acad Sci U S A. 2015; 112: 1392-1397.

Migita T, Oda Y, Naito S, Morikawa W, Kuwano M, Tsuneyoshi M. The accumulation of angiostatin-like fragments in human prostate carcinoma. Clin Cancer Res. 2001; 7: 2750–2756.

Wang H, Doll JA, Jiang K, et al. Differential binding of plasminogen, plasmin, and angiostatin 4.5 to cell surface beta-actin: implications for cancer-mediated angiogenesis. Cancer Res. 2006; 66: 7211–7215.

Heidtmann HH, Nettelbeck DM, Mingels A, Jäger R, Welker HG, Kontermann RE.. Generation of angiostatin-like fragments from plasminogen by prostate-specific antigen. Br J Cancer. 1999; 81: 1269–1273.

Firlej V, Mathieu JR, Gilbert C et al. Thrombospondin-1 triggers cell migration and development of advanced prostate tumors. Cancer Res. 2011; 71: 7649–58.

Rofstad EK, Henriksen K, Galappathi K, Mathiesen B. Antiangiogenic treatment with throm-bospondin-1 enhances primary tumor radiation response and prevents growth of dormant pulmonary micrometastases after curative radiation therapy in human melanoma xenografts. Cancer Res. 2003; 63: 4055–4061.

DOI: http://dx.doi.org/10.22037/uj.v0i0.4282


  • There are currently no refbacks.