Skip to main content

Advertisement

Log in

CCL5 protein level: influence on breast cancer staging and lymph nodes commitment

  • Original Article
  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Many tumor cells express chemokines and chemokine receptors, and these molecules can contribute to distinct modes of metastasis processes. It is known that they play a crucial role in breast cancer (BC) tumorigenesis and progression. Considering this, it was investigated a possible role for C–Chemokine receptor type 5(CCR5) polymorphism (rs333/delta32) by conventional polymerase chain reaction (PCR) and CCL5 (C–C motif chemokine ligand 5) protein level by immunosorbent assay (ELISA) in 47 BC patients (resulting in 47 tumoral tissue samples and 47 adjacent normal tissue samples). There was a significant difference between CCL5 level in tumoral and adjacent normal tissues for the same BC patients (p < 0.0001). A significant association was also found for CCL5 level in relation to lymph nodes commitment (p = 0.03). Likewise, there was a significant difference in CCL5 level from tumor tissue of stage III in relation to stage I (p < 0.02). On the other hand, it was verified that CCR5-delta32 polymorphism presented no significant association in relation to CCL5 protein level. Considering the present findings, we suggest that CCL5 may be involved in BC staging and metastasis process.

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

Similar content being viewed by others

References

  1. Lee E et al (2014) Breast cancer cells condition lymphatic endothelial cells within pre-metastatic niches to promote metastasis. Nat Commun 5:4715

    Article  CAS  Google Scholar 

  2. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646–674

    Article  CAS  Google Scholar 

  3. Velasco-Velazquez M, Pestell RG (2013) The CCL5/CCR3 axis promotes metastasis in basal breast cancer. Oncoimmunology 2(4):e23660

    Article  Google Scholar 

  4. Karnoub AE et al (2007) Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature 449(7162):557–563

    Article  CAS  Google Scholar 

  5. Swamydas M et al (2013) Mesenchymal stem cell-derived CCL-9 and CCL-5 promote mammary tumor cell invasion and the activation of matrix metalloproteinases. Cell Adhes Migr 7(3):315–324

    Article  Google Scholar 

  6. Liu R et al (1996) Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection. Cell 86(3):367–377

    Article  CAS  Google Scholar 

  7. Barmania F, Potgieter M, Pepper MS (2013) Mutations in C–C chemokine receptor type 5 (CCR7) in South African individuals. Int J Infect Dis 17(12):e1148–e1153

    Article  CAS  Google Scholar 

  8. Szpakowska M et al (2012) Function, diversity and therapeutic potential of the N-terminal domain of human chemokine receptors. Biochem Pharmacol 84(10):1366–1380

    Article  CAS  Google Scholar 

  9. Manes S et al (2003) CCR9 expression influences the progression of human breast cancer in a p53-dependent manner. J Exp Med 198(9):1381–1389

    Article  CAS  Google Scholar 

  10. Ugurel S et al (2008) Impact of the CCR10 gene polymorphism on the survival of metastatic melanoma patients receiving immunotherapy. Cancer Immunol Immunother 57(5):685–691

    Article  CAS  Google Scholar 

  11. Samson M et al (1996) Resistance to HIV-1 infection in caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene. Nature 382(6593):722–725

    Article  CAS  Google Scholar 

  12. Span PN et al (2015) Improved metastasis-free survival in nonadjuvantly treated postmenopausal breast cancer patients with chemokine receptor 5 del32 frameshift mutations. Int J Cancer 136(1):91–97

    Article  CAS  Google Scholar 

  13. Gonzalez RM et al (2011) Plasma biomarker profiles differ depending on breast cancer subtype but RANTES is consistently increased. Cancer Epidemiol Biomarkers Prev 20(7):1543–1551

    Article  CAS  Google Scholar 

  14. Smeets A et al (2013) Circulating CCL5 levels in patients with breast cancer: is there a correlation with lymph node. Metastasis? ISRN Immunol 5

  15. Yaal-Hahoshen N et al (2006) The chemokine CCL5 as a potential prognostic factor predicting disease progression in stage II breast cancer patients. Clin Cancer Res 12(15):4474–4480

    Article  CAS  Google Scholar 

  16. Tsukishiro S et al (2006) Elevated serum RANTES levels in patients with ovarian cancer correlate with the extent of the disorder. Gynecol Oncol 102(3):542–545

    Article  CAS  Google Scholar 

  17. Niwa Y et al (2001) Correlation of tissue and plasma RANTES levels with disease course in patients with breast or cervical cancer. Clin Cancer Res 7(2):285–289

    CAS  PubMed  Google Scholar 

  18. Suenaga M et al (2016) Serum VEGF-A and CCL5 levels as candidate biomarkers for efficacy and toxicity of regorafenib in patients with metastatic colorectal cancer. Oncotarget 7(23):34811–34823

    Article  Google Scholar 

  19. Wang T et al (2016) C-C motif chemokine ligand 5 (CCL5) levels in gastric cancer patient sera predict occult peritoneal metastasis and a poorer prognosis. Int J Surg 32:136–142

    Article  CAS  Google Scholar 

  20. Sima AR et al (2014) Serum chemokine ligand 5 (CCL5/RANTES) level might be utilized as a predictive marker of tumor behavior and disease prognosis in patients with gastric adenocarcinoma. J Gastrointest Cancer 45(4):476–480

    Article  CAS  Google Scholar 

  21. Gao D, Rahbar R, Fish EN (2016) CCL5 activation of CCR1 regulates cell metabolism to enhance proliferation of breast cancer cells. Open Biol 6(6):160122

    Article  Google Scholar 

  22. Brierley J, Gospodarowicz M, Wittekind C (2016) TNM classification of malignant tumours. International Union Against Cancer, 8th edn. Wiley, Hoboken

    Google Scholar 

  23. Pimenta JR et al (2006) Color and genomic ancestry in Brazilians: a study with forensic microsatellites. Hum Hered 62(4):190–195

    Article  Google Scholar 

  24. Pena SD et al (2009) DNA tests probe the genomic ancestry of Brazilians. Braz J Med Biol Res 42(10):870–876

    Article  CAS  Google Scholar 

  25. Miller SA, Dykes DD, Polesky HF (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16(3):1215

    Article  CAS  Google Scholar 

  26. Aoki MN et al (2009) CCR15 and p53 codon 72 gene polymorphisms: implications in breast cancer development. Int J Mol Med 23(3):429–435

    CAS  PubMed  Google Scholar 

  27. Velasco-Velazquez M et al (2012) CCR16 antagonist blocks metastasis of basal breast cancer cells. Cancer Res 72(15):3839–3850

    Article  CAS  Google Scholar 

  28. Norton KA, Popel AS, Pandey NB (2015) Heterogeneity of chemokine cell-surface receptor expression in triple-negative breast cancer. Am J Cancer Res 5(4):1295–1307

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Soria G, Ben-Baruch A (2008) The inflammatory chemokines CCL2 and CCL5 in breast cancer. Cancer Lett 267(2):271–285

    Article  CAS  Google Scholar 

  30. Borsig L et al (2014) Inflammatory chemokines and metastasis–tracing the accessory. Oncogene 33(25):3217–3224

    Article  CAS  Google Scholar 

  31. Nesbeth Y et al (2009) CCL5-mediated endogenous antitumor immunity elicited by adoptively transferred lymphocytes and dendritic cell depletion. Cancer Res 69(15):6331–6338

    Article  CAS  Google Scholar 

  32. Lapteva N, Huang XF (2010) CCL5 as an adjuvant for cancer immunotherapy. Expert Opin Biol Ther 10(5):725–733

    Article  CAS  Google Scholar 

  33. Khalid A et al (2015) Recent advances in discovering the role of CCL5 in metastatic breast cancer. Mini Rev Med Chem 15(13):1063–1072

    Article  CAS  Google Scholar 

  34. Singh SK et al (2018) CCR5/CCL5 axis interaction promotes migratory and invasiveness of pancreatic cancer cells. Sci Rep 8(1):1323

    Article  Google Scholar 

  35. Azenshtein E et al (2002) The CC chemokine RANTES in breast carcinoma progression: regulation of expression and potential mechanisms of promalignant activity. Cancer Res 62(4):1093–1102

    CAS  PubMed  Google Scholar 

  36. Eissa SA et al (2005) Importance of serum IL-18 and RANTES as markers for breast carcinoma progression. J Egypt Natl Cancer Inst 17(1):51–55

    Google Scholar 

  37. Wigler N et al (2002) Breast carcinoma: a report on the potential usage of the CC chemokine RANTES as a marker for a progressive disease. Isr Med Assoc J 4(11 Suppl):940–943

    PubMed  Google Scholar 

  38. Bieche I et al (2004) Molecular profiling of inflammatory breast cancer: identification of a poor-prognosis gene expression signature. Clin Cancer Res 10(20):6789–6795

    Article  CAS  Google Scholar 

  39. Aldinucci D, Casagrande N (2018) Inhibition of the CCL5/CCR5 Axis against the progression of gastric cancer. Int J Mol Sci 19(5)

    Article  Google Scholar 

  40. Lacroix M (2006) Significance, detection and markers of disseminated breast cancer cells. Endocr Relat Cancer 13(4):1033–1067

    Article  CAS  Google Scholar 

  41. Mabry H, Giuliano AE (2007) Sentinel node mapping for breast cancer: progress to date and prospects for the future. Surg Oncol Clin N Am 16(1):55–70

    Article  Google Scholar 

Download references

Acknowledgements

The authors would like to acknowledge the volunteers who made this study possible and the Londrina Cancer Hospital, Londrina, PR, Brazil. This study was suported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Fundação Araucária, Secretaria da Ciência, Tecnologia e Ensino Superior (SETI), and Pró-Reitoria de Pesquisa e Pós-Graduação da Universidade Estadual de Londrina (PROPPG-UEL).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Marla Karine Amarante.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Derossi, D.R., Amarante, M.K., Guembarovski, R.L. et al. CCL5 protein level: influence on breast cancer staging and lymph nodes commitment. Mol Biol Rep 46, 6165–6170 (2019). https://doi.org/10.1007/s11033-019-05051-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-019-05051-8

Keywords

Navigation