Skip to main content
SpringerLink
Log in

Overexpression of CXCL3 can enhance the oncogenic potential of prostate cancer

  • Urology - Original Paper
  • Published:
International Urology and Nephrology Aims and scope Submit manuscript

Abstract

Purpose

CXCL3 and its receptor CXCR2 were considered to play particularly important roles in the progression of malignancies. However, the investigations about CXCL3/CXCR2 axis in prostate cancer have been poorly involved. Herein we firstly reported our studies on the expression and biological roles of CXCL3 and CXCR2 in prostate cancer.

Methods

Expression levels of CXCL3 and CXCR2 in prostate cancer cell lines (PC-3, DU145 and LNCaP), immortalized prostate stromal cell line (WPMY-1) and immortalized prostate epithelial cell line (RWPE-1) were investigated by RT-PCR, ELISA and western blot, whereas expression levels of CXCL3 in a prostate tissue microarray were detected by immunohistochemistry. Cell counting kit-8 and transwell assays were, respectively, utilized to determine the effects of exogenous CXCL3 on the cell proliferation and migration. We further examined whether CXCL3 could regulate the expression of genes correlated with prostate tumorigenesis by RT- PCR.

Results

Elevated expression of CXCR2 was detected in DU145, LNCaP and RWPE-1. Moreover, high-level CXCL3 can be secreted by PC-3 and RWPE-1, and CXCL3 protein expression level in tissue microarray is concordant with prostate cancer metastasis. Exogenous CXCL3 does not contribute to proliferation, but has a significant effect on migration of prostate cancer cells and RWPE-1. Finally, our data showed that exogenous CXCL3 can regulate the expression of genes including ERK, TP73, NUMB, BAX and NDRG3.

Conclusion

Our findings suggest that CXCL3 and its receptor CXCR2 are overexpressed in prostate cancer cells, prostate epithelial cells and prostate cancer tissues, which may play multiple roles in prostate cancer progression and metastasis.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. American Cancer Society (2012) Cancer facts and figures. American Cancer Society, Atlanta, GA

    Google Scholar 

  2. Ferlay J, Steliarova-Foucher E, Lortet-tieulent J, Rosso S, Coebergh JW, Comber H, Forman D, Bray F (2013) Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer 49(6):1374–1403

    Article  CAS  PubMed  Google Scholar 

  3. Ren SC, Chen R, Sun YH (2013) Prostate cancer research in China. Asian J androl 15(3):350–353

    Article  PubMed  PubMed Central  Google Scholar 

  4. Mantovani A, Bonecchi R, Locati M (2006) Tuning inflammation and immunity by chemokine sequestration: decoys and more. Nat Rev Immunol 6(12):907–918

    Article  CAS  PubMed  Google Scholar 

  5. Keane MP, Arenberg DA, Moore BB, Addison CL, Strieter RM (1998) CXC chemokines and angiogenesis/angiostasis. Proc Assoc Am Phys 110(4):288–296

    CAS  PubMed  Google Scholar 

  6. Engl T, Relja B, Blumenberg C, Müller I, Ringel EM, Beecken WD, Jonas D, Blaheta RA (2006) Prostate tumor CXC-chemokine profile correlates with cell adhesion to endothelium and extracellular matrix. Life Sci 78(16):1784–1793

    Article  CAS  PubMed  Google Scholar 

  7. Singh RK, Lokeshwar BL (2011) The IL-8-regulated chemokine receptor CXCR7 stimulates EGFR signaling to promote prostate cancer growth. Cancer Res 71(9):3268–3277

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Kogan-Sakin I, Cohen M, Paland N, Madar S, Solomon H, Molchadsky A, Brosh R, Buganim Y, Goldfinger N, Klocker H, Schalken JA, Rotter V (2009) Prostate stromal cells produce CXCL-1, CXCL-2, CXCL-3 and IL-8 in response to epithelia-secreted IL-1. Carcinogenesis 30(4):698–705

    Article  CAS  PubMed  Google Scholar 

  9. See AL, Chong PK, Lu SY, Lim YP (2014) CXCL3 is a potential target for breast cancer metastasis. Curr Cancer Drug Targets 14(3):294–309

    Article  PubMed  Google Scholar 

  10. Wente MN, Keane MP, Burdick MD, Friess H, Büchler MW, Ceyhan GO, Reber HA, Strieter RM, Hines OJ (2006) Blockade of the chemokine receptor CXCR2 inhibits pancreatic cancer cell-induced angiogenesis. Cancer Lett 241(2):221–227

    Article  CAS  PubMed  Google Scholar 

  11. Mestas J, Burdick MD, Reckamp K, Pantuck A, Figlin RA, Strieter RM (2005) The role of CXCR2/CXCR2 ligand biological axis in renal cell carcinoma. J Immunol 175(8):5351–5357

    Article  CAS  PubMed  Google Scholar 

  12. Murphy C, McGurk M, Pettigrew J, Santinelli A, Mazzucchelli R, Johnston PG, Montironi R, Waugh DJ (2005) Nonapical and cytoplasmic expression of interleukin-8, CXCR1, and CXCR2 correlates with cell proliferation and microvessel density in prostate cancer. Clin Cancer Res 11(11):4117–4127

    Article  CAS  PubMed  Google Scholar 

  13. Huang X, Chen S, Xu L, Liu Y, Deb DK, Platanias LC, Bergan RC (2005) Genistein inhibits p38 map kinase activation, matrix metalloproteinase type 2, and cell invasion in human prostate epithelial cells. Cancer Res 65(8):3470–3478

    CAS  PubMed  Google Scholar 

  14. Wang CJ, Zhou ZG, Holmqvist A, Zhang H, Li Y, Adell G, Sun XF (2009) Survivin expression quantified by Image Pro-Plus compared with visual assessment. Appl Immunohistochem Mol Morphol 17(6):530–535

    Article  CAS  PubMed  Google Scholar 

  15. Singh S, Singh R, Singh UP, Rai SN, Novakovic KR, Chung LW, Didier PJ, Grizzle WE, Lillard JW Jr (2009) Clinical and biological significance of CXCR5 expressed by prostate cancer specimens and cell lines. Int J Cancer 125(10):2288–2295

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Bièche I, Chavey C, Andrieu C, Busson M, Vacher S, Le Corre L, Guinebretière JM, Burlinchon S, Lidereau R, Lazennec G (2007) CXC chemokines located in the 4q21 region are up-regulated in breast cancer. Endocr Relat Cancer 14(4):1039–1052

    Article  PubMed  Google Scholar 

  17. Moore BB, Arenberg DA, Stoy K, Morgan T, Addison CL, Morris SB, Glass M, Wilke C, Xue YY, Sitterding S, Kunkel SL, Burdick MD, Strieter RM (1999) Distinct CXC chemokines mediate tumorigenicity of prostate cancer cells. Am J Pathol 154(5):1503–1512

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Begley LA, Kasina S, Mehra R, Adsule S, Admon AJ, Lonigro RJ, Chinnaiyan AM, Macoska JA (2008) CXCL5 promotes prostate cancer progression. Neoplasia 10(3):244–254

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Begley LA, Kasina S, MacDonald J (2008) The inflammatory microenvironment of the aging prostate facilitates cellular proliferation and hypertrophy. Cytokine 43(2):194–199

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Benelli R, Stigliani S, Minghelli S, Carlone S, Ferrari N (2013) Impact of CXCL1 overexpression on growth and invasion of prostate cancer cell. Prostate 73(9):941–951

    Article  CAS  PubMed  Google Scholar 

  21. Farioli-Vecchioli S, Cinà I, Ceccarelli M, Micheli L, Leonardi L, Ciotti MT, De Bardi M, Di Rocco C, Pallini R, Cavallaro S, Tirone F (2012) Tis21 knock-out enhances the frequency of medulloblastoma in Patched1 heterozygous mice by inhibiting the Cxcl3-dependent migration of cerebellar neurons. J Neurosci 32(44):15547–15564

    Article  CAS  PubMed  Google Scholar 

  22. Song X, Wang Y, Du H, Fan Y, Yang X, Wang X, Wu X, Luo C (2014) Overexpression of HepaCAM inhibits cell viability and motility through suppressing nucleus translocation of androgen receptor and ERK signaling in prostate cancer. Prostate 74(10):1023–1033

    Article  CAS  PubMed  Google Scholar 

  23. Bisso A, Collavin L, Del Sal G (2011) p73 as a pharmaceutical target for cancer therapy. Curr Pharm Des 17(6):578–590

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Singh AP, Bafna S, Chaudhary K, Venkatraman G, Smith L, Eudy JD, Johansson SL, Lin MF, Batra SK (2008) Genome-wide expression profiling reveals transcriptomic variation and perturbed gene networks in androgen-dependent and androgen-independent prostate cancer cells. Cancer Lett 259(1):28–38

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Wang W, Li Y, Li Y, Hong A, Wang J, Lin B, Li R (2009) NDRG3 is an androgen regulated and prostate enriched gene that promotes in vitro and in vivo prostate cancer cell growth. Int J Cancer 124(3):521–530

    Article  CAS  PubMed  Google Scholar 

  26. Flores AN, McDermott N, Meunier A, Marignol L (2014) NUMB inhibition of NOTCH signalling as a therapeutic target in prostate cancer. Nat Rev Urol 11(9):499–507

    Article  CAS  PubMed  Google Scholar 

  27. Carter S, Vousden KH (2008) A role for Numb in p53 stabilization. Genome Biol 9(5):221

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

The study was financially supported by Grants from National Nature Science Foundation of China (No. 81272854), Nature Science Foundation of Heilongjiang Province (No. D201129), Key Research Program of Jiamusi University (No. Sz2009-008), Science and Innovation Team Foundation of Jiamusi University (No. cxtd-2013-04), President Innovation and Entrepreneurship Foundation of Jiamusi University (No. xzyf2014-12) and Postgraduate Science and Innovation Foundation of Jiamusi University (No. LZR2015_011).

Author information

Authors and Affiliations

  1. Department of Urology, The First Affiliated Hospital, Jiamusi University, Jiamusi, Heilongjiang, China

    Shi-liang Gui

  2. Department of Urology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China

    Li-chen Teng

  3. Basic Medical College, Jiamusi University, Jiamusi, Heilongjiang, China

    Shu-qiu Wang, Shuang Liu, Xiao-lian Zhao, Lei Liu, Hong-yu Sui, Yang Yang, Li-chun Liang, Mo-lin Wang, Xin-yi Li, Yu Cao, Feng-ying Li & Wei-qun Wang

  4. Department of Urology, Affiliated Xuzhou Hospital of Jiangsu University (Xuzhou Cancer Hospital), Xuzhou, Jiangsu, China

    Ying-Li Lin

Authors
  1. Shi-liang Gui
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Li-chen Teng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shu-qiu Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shuang Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ying-Li Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xiao-lian Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Lei Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hong-yu Sui
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yang Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Li-chun Liang
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Mo-lin Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Xin-yi Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Yu Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Feng-ying Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Wei-qun Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Wei-qun Wang.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standards

The study was conducted in accordance with the ethical principles for medical research on human beings established by the 1964 Helsinki protocol, and was approved by the Institutional ethics committee (No. JMSU-188).

Additional information

Shi-liang Gui and Li-chen Teng are co-first authors.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gui, Sl., Teng, Lc., Wang, Sq. et al. Overexpression of CXCL3 can enhance the oncogenic potential of prostate cancer. Int Urol Nephrol 48, 701–709 (2016). https://doi.org/10.1007/s11255-016-1222-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11255-016-1222-2

Keywords

Search

Navigation