Circulating Nuclear Factor-Kappa B Mediates Cancer-Associated Inflammation in Human Breast and Colon Cancer

Nuclear factor-kappa B in breast and colon cancer

  • Hafize Uzun Istanbul University-Cerrahpasa
  • Berrin Papila Kundaktepe
  • Volkan Sozer
  • Pinar Kocael
  • Sinem Durmus
  • Dilara Kurtulus
  • Cigdem Papila
  • Remise Gelisgen
Keywords: Nuclear factor kappa-B, tumor necrosis factor-α, soluble TNF-related apoptosis inducing ligand, Interleukin-6, Pentraxin-3

Abstract


Background: Inflammation is recognized as a hallmark feature of cancer development and progression. The aim of our study was to investigate the significance of serum nuclear factor kappa-B (NF-кB) levels as a circulating marker in the monitor of inflammation in breast and colon cancer; to show the relationship between NF-кB with inflammatory parameters as tumor necros faktor-α (TNF-α), soluble TNF-related apoptosis inducing ligand (sTRAIL), interleukin-6 (IL-6), pentraxin-3 (PTX-3), procalcitonin (PCT), and C-reactive protein (CRP) levels. Methods: Serum NF-кB, TNF-α, sTRAIL, IL-6, PTX-3, PCT, and serum CRP levels were measured using enzyme linked immunosorbent assay (ELISA) in 40 patients with breast cancer, 40 patients with colon cancer and 30 healthy controls. Results: The serum NF-кB, TNF-α, IL-6, PTX-3, PCT and serum CRP concentration was significantly higher and the serum sTRAIL concentration was significantly lower in patients with breast and colon cancer than in those with an healthy controls. NF-кB were positive correlated with CRP and negative corelated with sTRAIL. Conclusions: These results suggest that increased NF-кB may decrease the clinical efficacy of sTRAIL in solid tumour cells. There is relationship between inflammation and carcinogenesis so that the development of cancer occurs with chronic inflammation in breast and colon. The study results have shown that colon and breast cancer patients have increased systemic inflammation, as measured by increased circulating cytokines, and acute phase proteins, or by abnormalities in circulating cells. NF-кB may combine with other markers of the systemic inflammatory response in prognostic scores in cancer. In addition to surgical resection of the tumor, conventional radio- and chemotherapy for cancer treatment, the use of sTRAIL or other agonists for cancer therapy appeared a new potential therapy.

 

References

1. Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008; 454: 436-44.
2. West NR, McCuaig S, Franchini F, Powrie F. Emerging cytokine networks in colorectal cancer. Nat Rev Immunol. 2015; 15: 615-29.
3. Hoesel B, Schmid JA. The complexity of NF-κB signaling in inflammation and cancer. Mol Cancer. 2013; 12: 86.
4. Perkins ND. Integrating cell-signalling pathways with NF-kappaB and IKK function. Nat Rev Mol Cell Biol. 2007; 8: 49-62.
5. Wu Y, Zhou BP. TNF-alpha/NF-kappaB/Snail pathway in cancer cell migration and invasion. Br J Cancer. 2010; 102: 639-44.
6. Allin KH, Nordestgaard BG. Elevated C-reactive protein in the diagnosis, prognosis, and cause of cancer. Crit Rev Clin Lab Sci. 2011; 48: 155-70.
7. Zhou B, Shu B, Yang J, Liu J, Xi T, Xing Y. C-reactive protein, interleukin-6 and the risk of colorectal cancer: a meta-analysis. Cancer Causes Control. 2014; 25: 1397-405.
8. Guo L, Liu S, Zhang S, Chen Q, Zhang M, Quan P, Lu J, Sun X. C-reactive protein and risk of breast cancer: A systematic review and meta-analysis. Sci Rep. 2015; 5: 10508.
9. Lussana F, Rambaldi A. Inflammation and myeloproliferative neoplasms J Autoimmun. 2017 Dec;85:58-63.
10. Sbrana A, Torchio M, Comolli G, Antonuzzo A, Danova M; Italian Network for Supportive Care in Oncology (NICSO). Use of procalcitonin in clinical oncology: a literature review. New Microbiol. 2016; 39: 174-180.
11. Mérino D1, Lalaoui N, Morizot A, Solary E, Micheau O. TRAIL in cancer therapy: present and future challenges. Expert Opin Ther Targets. 2007; 11: 1299-314.
12. Prajoko YW, Aryandono T Expression of nuclear factor kappa B (NF-κB) as a predictor of poor pathologic response to chemotherapy in patients with locally advanced breast cancer.. Asian Pac J Cancer Prev. 2014; 15: 595-8.
13. Coussens LM Werb Z. Inflammation and cancer. Nature 2002; 420: 860-867.
14. Shacter E, Weitzman SA. Chronic Inflammation and Cancer. Oncology 2002; 16: 217–226.
15. Lin WW, Karin M. A cytokine-mediated link between innate immunity, inflammation, and cancer. J Clin Invest 2007; 11: 1175-1183.
16. Germano G, Allavena P, Mantovani A. Cytokines as a key component of cancer-related inflammation. Cytokine. 2008; 43: 374-9.
17. Kim S, Keku TO, Martin C, Galanko J, Woosley JT, Schroeder JC, Satia JA, Halabi S, Sandler RS. Circulating levels of inflammatory cytokines and risk of colorectal adenomas. Cancer Res. 2008; 68: 323-8.
18. Soria G, Ofri-Shahak M, Haas I, Yaal-Hahoshen N, Leider-Trejo L, Leibovich-Rivkin T, Weitzenfeld P, Meshel T, Shabtai E, Gutman M, Ben-Baruch A. Inflammatory mediators in breast cancer: coordinated expression of TNF- & IL-1β with CCL2 & CCL5 and effects on epithelial-to-mesenchymal transition. BMC Cancer. 2011; 11: 130.
19. Madhusudan S1, Muthuramalingam SR, Braybrooke JP, Wilner S, Kaur K, Han C, Hoare S, Balkwill F, Ganesan TS. Study of etanercept, a tumor necrosis factor-alpha inhibitor, in recurrent ovarian cancer. J Clin Oncol. 2005; 23: 5950-9.
20. Salgado R, Junius S, Benoy I, Van Dam P, Vermeulen P, Van Marck E, Huget P, Dirix LY. Circulating interleukin-6 predicts survival in patients with metastatic breast cancer. Int J Cancer. 2003; 103: 642-6.
21. Xu J1, Ye Y, Zhang H, Szmitkowski M, Mäkinen MJ, Li P, Xia D, Yang J, Wu Y, Wu H. Diagnostic and prognostic value of serum ınterleukin-6 in colorectal cancer. Medicine (Baltimore). 2016; 95: e2502.
22. Shiga K, Hara M, Nagasaki T, Sato T, Takahashi H, Sato M, Takeyama H. Preoperative Serum Interleukin-6 Is a Potential Prognostic Factor for Colorectal Cancer, including Stage II Patients. Gastroenterol Res Pract. 2016; 2016: 9701574.
23. Chung YC, Chaen YL, Hsu CP. Clinical significance of tissue expression of interleukin-6 in colorectal carcinoma. Anticancer Res. 2006; 26: 3905-11.
24. Kinoshita T, Ito H, Miki C. Serum interleukin-6 level reflects the tumor proliferative activity in patients with colorectal carcinoma. Cancer. 1999; 85: 2526-31.
25. Chung YC, Chang YF. Serum interleukin-6 levels reflect the disease status of colorectal cancer. J Surg Oncol. 2003; 83: 222-6.
26. Yeh KY, Li YY, Hsieh LL, Lu CH, Chou WC, Liaw CC, Tang RP, Liao SK. Analysis of the effect of serum interleukin-6 (IL-6) and soluble IL-6 receptor levels on survival of patients with colorectal cancer. Jpn J Clin Oncol. 2010; 40: 580-7.
27. Berberoglu U, Yildirim E, Celen O. Serum levels of tumor necrosis factor alpha correlate with response to neoadjuvant chemotherapy in locally advanced breast cancer. Int J Biol Markers. 2004; 19: 130-4.
28. Stanilov N, Miteva L, Dobreva Z, Stanilova S. Colorectal cancer severity and survival in correlation with tumour necrosis factor-alpha. Biotechnol Biotechnol Equip. 2014; 28: 911-917.
29. Grimm M, Lazariotou M, Kircher S, H€ofelmayr A, Germer CT, von Rahden BHA, Waaga-Gasser AM, Gasser M. Tumor necrosis factor-a is associated with positive lymph node status in patients with recurrence of colorectal cancer - indications for anti-TNF- agents in cancer treatment. Cell Oncol. 2010; 33: 151-163.
30. Sharma R, Zucknick M, London R, Kacevska M, Liddle C, Clarke S. Systemic inflammatory response predicts prognosis in patients with advanced-stage colorectal cancer. Clin Colorectal Cancer. 2008; 7: 331-337.
31. Tang D, Tao D, Fang Y, Deng C, Xu Q, Zhou J. TNF-Alpha Promotes Invasion and Metastasis via NF-Kappa B Pathway in Oral Squamous Cell Carcinoma. Med Sci Monit Basic Res. 2017; 23: 141-149.
32. Walczak H, Miller RE, Ariail K, Gliniak B, Griffith TS, Kubin M, Chin W, Jones J, Woodward A, Le T, Smith C, Smolak P, Goodwin RG, Rauch CT, Schuh JC, Lynch DH. Tumoricidal activity of tumor necrosis factor-related apoptosis-inducing ligand in vivo. Nat Med. 1999; 5: 157-63.
33. Kelley SK1, Harris LA, Xie D, Deforge L, Totpal K, Bussiere J, Fox JA. Preclinical studies to predict the disposition of Apo2L/tumor necrosis factor-related apoptosis-inducing ligand in humans: characterization of in vivo efficacy, pharmacokinetics, and safety. J Pharmacol Exp Ther. 2001; 299: 31-8.
34. Naka T, Sugamura K, Hylander BL, Widmer MB, Rustum YM, Repasky EA. Effects of tumor necrosis factor-related apoptosis-inducing ligand alone and in combination with chemotherapeutic agents on patients' colon tumors grown in SCID mice. Cancer Res. 2002; 62: 5800-6.
35. Toiyama D, Takaha N, Shinnoh M, Ueda T, Kimura Y, Nakamura T, Hongo F, Mikami K, Kamoi K, Kawauchi A, Miki T. Significance of serum tumor necrosis factor-related apoptosis-inducing ligand as a prognostic biomarker for renal cell carcinoma. Mol Clin Oncol. 2013; 1: 69-74.
36. Tecchio C, Huber V, Scapini P, et al: IFNalpha-stimulated neutro-phils and monocytes release a soluble form of TNF-related apoptosis-inducing ligand (TRAIL/Apo-2 ligand) displaying apoptotic activity on leukemic cells. Blood 103: 3837-3844, 2004.
37. Tanaka H, Ito T, Kyo T and Kimura A: Treatment with IFNalpha in vivo up-regulates serum-soluble TNF-related apoptosis inducing ligand (sTRAIL) levels and TRAIL mRNA expressions in neutrophils in chronic myelogenous leukemia patients. Eur J Haematol 2007; 78: 389-398,.
38. Perik PJ, Van der Graaf WT, De Vries EG, et al: Circulating apoptotic proteins are increased in long-term disease-free breast cancer survivors. Acta Oncol 45: 175-183, 2006.
39. Luo JL, Maeda S, Hsu LC, et al. Inhibition of NF-kappaB in cancer cells converts inflammation-induced tumor growth mediated by TNFalpha to TRAIL-mediated tumor regression. Cancer Cell 2004; 6: 297–305
40. Kwon HC, Kim SH, Oh SY, Lee S, Kwon KA, Lee JH, Choi HJ, Park KJ, Lee HS, Roh MS, Kim HJ. Clinicopathological significance of nuclear factor-kappa B, HIF-1 alpha, and vascular endothelial growth factor expression in stage III colorectal cancer. Cancer Sci. 2010; 101: 1557-61.
41. Slattery ML, Mullany LE, Sakoda L, Samowitz WS, Wolff RK, Stevens JR, Herrick JS. The NF-κB signalling pathway in colorectal cancer: associations between dysregulated gene and miRNA expression. J Cancer Res Clin Oncol. 2018;144: 269-283.
42. Giacomini A, Ghedini GC, Presta M, Ronca R. Long pentraxin 3: a novel multifaceted player in cancer. Biochim Biophys Acta Rev Cancer. (2018); 1869: 53-63.
43. Diamandis EP, Goodglick L, Planque C, Thornquist MD. Pentraxin-3 is a novel biomarker of lung carcinoma. Clin Cancer Res. 2011;17: 2395–9.
44. Choi B, Lee E-J, Song D-H, Yoon S-C, Chung Y-H, Jang Y, et al. Elevated pentraxin 3 in bone metastatic breast cancer is correlated with osteolytic function. Oncotarget. 2014; 5: 481-92.
45. Chen WY, Wu F, You ZY, Zhang ZM, Guo YL, Zhong LX. Analyzing the differentially expressed genes and pathway cross-talk in aggressive breast cancer. J Obstet Gynaecol Res. 2015; 41: 132–40.
46. Player A, Abraham N, Burrell K, Bengone IO, Harris A, Nunez L, et al. Identification of candidate genes associated with triple negative breast cancer. Genes Cancer. 2017; 8: 659-72.
47. Basu S, Harris H, Wolk A, Rossary A, Caldefie-Chézet F, Vasson MP, Larsson A. Inflammatory F2-isoprostane, prostaglandin F2α, pentraxin 3 levels and breast cancer risk: The Swedish Mammography Cohort. Prostaglandins Leukot Essent Fatty Acids. 2016; 113: 28-32.
48. Zhang J, Wang TY, Niu XC. Increased plasma levels of Pentraxin 3 are associated with poor prognosis of colorectal carcinoma patients. Tohoku J Exp Med. 2016; 240: 39-46.
49. Liu B, Zhao Y, Guo L. Increased serum pentraxin-3 level predicts poor prognosis in patients with colorectal cancer after curative surgery, a cohort study. Medicine. 2018; 97: e11780.
50. Durnaś B, Wątek M, Wollny T, Niemirowicz K, Marzec M, Bucki R, Góźdź S. Utility of blood procalcitonin concentration in the management of cancer patients with infections. Onco Targets Ther. 2016; 9: 469-75.
Published
2020/09/11
Section
Original paper