Abstract
Up-regulation of the IL-1-IL-6 network stimulates systemic expression of C-reactive protein (CRP).This cytokine network system plays a pivotal role in inducing angiogenic growth factors in in-testinalmucosa. Serum CRP level and tissue concentrations of cytokines in colorectal cancerpatients were determined and an in vitro model was employed to determine the time course ofinduction of IL-6 in Caco-2 cells. Increased serum CRP was associated with recurrent diseaseand shorter survival time. Intense surgical stress and the presence of an acute phase reactantwere independently associated with overexpression of IL-6 in the tumor. Enhanced IL-6 pro-teinexpression in Caco-2 cells induced by the initial treatment with IL-1β or lipopolysaccha-ridecould be abrogated by additional presupplementation of IL-1ra. The presence of an acutephase reactant reflects uncontrolled up-regulation of the local IL-1-IL-6 network system in thetumor, which may enhance the survival and proliferation of remnant cancer cells after tumorresection.
Similar content being viewed by others
REFERENCES
Du Clos TW: Function of C-reactive protein. Ann Med 32(4): 274–278, 2000
McMillan DC, Wotherspoon HA, Fearon KC, Sturgeon C, Cooke TG, McArdle CS: A prospective study of tumor recurrence and the acute-phase response after apparently curative colorectal cancer surgery. Am J Surg 170(4): 319–322, 1995
Nozoe T, Matsumata T, Kitamura M, Sugimachi K: Significance of preoperative elevation of serum C-reactive protein as an indicator for prognosis in colorectal cancer. AmJ Surg 178(4): 335–338, 1998
Fransen EJ, Maessen JG, Elenbaas TW, van Aarnhem EE, van Dieijen-Visser MP: Enhanced preoperative C-reactive protein plasma levels as a risk factor for postoperative infections after car-diac surgery. Ann Thorac Surg 67(1): 134–138, 1999
Haupt W, Hohenberger W, Mueller R, Klein P, Christou NV: Association between preoperative acute phase response and postoperative complications. Eur J Surg 163(1): 39–44, 1997
Parikh AA, Salzman AL, Fisher JE, Szabo C, Hasselgren PO: Interleukin-1β and interferon-γ° regulate interleukin-6 production in cultured human intestinal epithelial cells. Shock 8(4): 249–255, 1997
Riche F, Dosquet C, Panis Y, Valleur P, Laisne MJ, Briard C, Wautier JL: Levels of portal and systemic blood cytokines after colectomy in patients with carcinoma or Crohn's disease. J Am Coll Surg 180(6): 718–724, 1995
Syk I, Hedges SR, Zederfeldt B, Risberg B: Enhanced cytokine response to surgical trauma in patients with colorectal cancer. Int J Surg Investig 1(3): 167–176, 1999
Oka M, Iizuka N, Yamamoto K, Gondo T, Abe T, Hazama S, Akitomi Y, Koishihara Y, Ohsugi Y, Ooba Y, Ishihara T, Suzuki T: The influence of interleukin-6 on the growth of human esophageal carcinoma cell lines. J Interferon Cytokine Res 16(6): 1001–1006, 1996
Kawano M, Hirano T, Matsuda T, Taga T, Horii Y, Iwato K, Asaoku H, Tang B, Tanabe O, Tanaka H: Autocrine generation and re-quirement of BSF-2/IL-6 for human multiple myelomas. Nature 332(6159): 83–85, 1988
Miki S, Iwano M, Miki Y, Yamamoto M, Tang B, Yokokawa K, Sonoda T, Hirano T, Kishimoto T: Interleukin-6 (IL-6) functions as an in vitro autocrine growth factor in renal cell carcinomas. FEBS Lett 250(2): 607–610, 1989
Ballou SP, Kushner I: Creactive protein and the acute phase re-sponse. Adv Intern Med 37(3): 313–316, 1992
Shimada H, Nabeya Y, Okazumi S, Matsubara H, Miyazawa Y, Shihratori T, Hayashi H, Aoki T, Sugaya M, Gunji Y, Kobayashi S, Ochiai T: Prognostic value of preoperative serum immunosup-pressive acidic protein in patients with esophageal squamous cell carcinoma. Dis Esophagus 16(2): 102–106, 2003
Kinoshita T, Ito H, Miki C: Serum interleukin-6 level reflects tumor proliferative activity in colorectal cancer patients. Cancer 85(12): 2526–2531, 1999
Miki C, Tonouchi H, Wakuda R, Hatada T, Inoue Y, Minato E, Kobayashi M, Kusunoki M: Intratumoral interleukin-6 down-regulation system and genetic mutations of tumor suppressor genes in colorectal carcinoma. Cancer 94(5): 1584–1592, 2002
Lu ZY, Bataille R, Poubelle P, Rapp MJ, Harousseau JL, Klein B: An interleukin 1 receptor antagonist blocks the IL-1-induced IL-6 paracrine production through a prostaglandin E2-related mechanism in multiple myeloma. Stem Cells 13(Suppl 2): 28–34, 1995
Ben-Eliyahu S: The promotion of tumor metastasis by surgery and stress: Immunological basis and implications for psychoneuroim-munology. Brain Behav Immun 17(Suppl 1): S27–S36, 2003
Tang R, Wang JY, Chien CR, Chen JS, Lin SE, Fan HA: The association between perioperative blood transfusion and survival of patients with colorectal cancer. Cancer 72: 341–348, 1993
Laurent C, Sa Cunha A, Couderc P, Rullier E, Saric J: Influence of postoperative morbidity on long-term survival following liver resection for colorectal metastases. Br J Surg 90: 1131–1136, 2003
Meta-Analysis Group in Cancer: Reappraisal of hepatic arterial in-fusion in the treatment of nonresectable liver metastases from col-orectal cancer. J Natl Cancer Inst 88: 252–258, 1996
Jee SH, Shen SC, Chiu HC, Tsai WL, Kuo M: Overexpression of interleukin-6 in human basal cell carcinoma cell lines increases anti-apoptotic activity and tumorigenic potency. Oncogene 20(2): 198–208, 2001
Frassanito MA, Cusmai A, Iodice G, Dammacco F: Au-tocrine interleukin-6 production and highly malignant multiple myeloma: Relation with resistance to drug-induced apoptosis. Blood 97(2): 483–489, 2001
Chauhan D, Kharbanda S, Ogata A, Urashima M, Teoh G, Robert-son M, Kufe DW, Anderson KC: Interleukin-6 inhibits Fas-induced apoptosis and stress-activated protein kinase activation in multiple myeloma cells. Blood 89(1): 227–234, 1997
Miyamoto Y, Hosotani R, Doi R, Wada M, Ida J, Tsuji S, Kawaguchi M, Nakajima S, Kobayashi H, Masui T, Imamura M: Interleukin-6 inhibits radiation induced apoptosis in pancreatic cancer cells. Anticancer Res 21(4A): 2449–2456, 2001
Woods KV, Adler-Storthz K, Clayman GL, Francis GM, Grimm EA: Interleukin-1 regulates interleukin-6 secretion in human oral squamous cell carcinoma in vitro: Possible influence of p53 but not human papillomavirus E6/E7. Cancer Res 58: 3142–3149, 1998
Lu ZY, Bataille R, Poubelle P, Rapp MJ, Harousseau JL, Klein B: An interleukin 1 receptor antagonist blocks the IL-1 induced IL-6 paracrine production through a prostaglandin E2-related mechanism in multiple myeloma. Stem Cells 2: 28–34, 1995
Yin M, Gopal V, Banavali S, Gartside P, Preisler H: Effects of an IL-1 receptor antagonist on acute myeloid leukemia cells. Leukemia 6: 898–901, 1992
Vidal-Vanaclocha F, Amezaga C, Asumendi A, et al.: Interleukin-1 receptor blockade reduces the number and size of murine B16 melanoma hepatic metastases. Cancer Res 54: 2667–2672, 1994
Rights and permissions
About this article
Cite this article
Miki, C., Konishi, N., Ojima, E. et al. C-Reactive Protein as a Prognostic Variable That Reflects Uncontrolled Up-Regulation of the IL-1-IL-6 Network System in Colorectal Carcinoma. Dig Dis Sci 49, 970–976 (2004). https://doi.org/10.1023/B:DDAS.0000034556.48527.6e
Issue Date:
DOI: https://doi.org/10.1023/B:DDAS.0000034556.48527.6e