Erdinç NAYIR, Ali ARICAN, Alper ATA, Sinan AYGÜN

Relationship Between IL-18 and Bone Metastasis in Female Breast Cancer

OBJECTIVEBreast cancer is a metastatic disease that frequently (in approximately 70% of cases) affects theskeletal system. The aim of the present study was to compare serum IL-18 levels in breast cancerpatients with and without bone metastases with healthy controls.METHODSIncluded were a total of 154 female breast cancer patients with bone metastases (n=53; Group 2) and withoutbone metastases (n=51; Group 1), as well as 50 healthy control subjects (Group 3). Serum IL-18 levels werecompared among the groups.RESULTSMean serum IL-18 levels were significantly different between Groups 1 and 3 (p

PDF

___

1. Anthony S. Fauci, Eugene Braunwald, Dennis L. Kasper Breast Cancer Harrison's Principles of internal Mehdicine 17th Ed. New York: The McGraw-Hill Companies, Inc. 2008.
2. Guise TA. Molecular mechanisms of osteolytic bone metastases. Cancer 2000;88(12 Suppl):2892-8.
3. Fisher B, Anderson S, Bryant J, Margolese RG, Deutsch M, et al. Twenty-Year Follow-up of a Randomized Trial Comparing Total Mastectomy, Lumpectomy, and Lumpectomy plus Irradiation for the Treatment of Invasive Breast Cancer. N Engl J Med 2002;347:1233-41.
4. Coleman RE. Clinical features of metastatic bone disease and risk of skeletal morbidity. Clin Cancer Res 2006;12(20 Suppl):6243-9.
5. Takubo T, Kumura T, Nakao T, Nakamae H, Aoyama Y, Nishiki S, et al. Comparative study on complete remission rate and overall survival in three groups classified based on the serum interleukin-18 level in non-Hodgkin's lymphoma patients. Acta Haematol 2000;104(4):220-2.
6. Eissa SA, Zaki SA, El-Maghraby SM, Kadry DY. Importance of serum IL-18 and RANTES as markers for breast carcinoma progression. J Egypt Natl Canc Inst 2005;17(1):51-5.
7. Günel N, Coşkun U, Sancak B, Günel U, Hasdemir O, Bozkurt S. Clinical importance of serum interleu- kin-18 and nitric oxide activities in breast carcinoma patients. Cancer 2002;95(3):663-7.
8. Eissa SA, Zaki SA, El-Maghraby SM, Kadry DY. Im- portance of serum IL-18 and RANTES as markers for breast carcinoma progression. J Egypt Natl Canc Inst 2005;17(1):51-5.
9. Okamoto M, Azuma K, Hoshino T, Imaoka H, Ike- da J, Kinoshita T, et al. Correlation of decreased survival and IL-18 in bone metastasis. Intern Med 2009;48(10):763-73.
10. Makiishi-Shimobayashi C1, Tsujimura T, Iwasaki T, Yamada N, Sugihara A, Okamura H, et al. Interleu- kin-18 up-regulates osteoprotegerin expression in stromal/osteoblastic cells. Biochem Biophys Res Com- mun 2001;281(2):361-6.
11. Udagawa N, Horwood NJ, Elliott J, Mackay A, Owens J, Okamura H, et al. Interleukin-18 (interferon-gam- ma-inducing factor) is produced by osteoblasts and acts via granulocyte/macrophage colony-stimulating factor and not via interferon-gamma to inhibit osteo- clast formation. J Exp Med 1997;185(6):1005-12.
12. Modrowski D, Lomri A, Marie PJ. Endogenous GM- CSF is involved as an autocrine growth factor for hu- man osteoblastic cells. J Cell Physiol 1997;170(1):35- 46.
13.Nakata A, Tsujimura T, Sugihara A, Okamura H, Iwa- saki T, Shinkai K, et al. Inhibition by interleukin 18 of osteolytic bone metastasis by human breast cancer cells. Anticancer Res 1999;19(5B):4131-8.
14. Iwasaki T, Yamashita K, Tsujimura T, Kashiwamura S, Tsutsui H, Kaisho T, et al. Interleukin-18 inhibits os- teolytic bone metastasis by human lung cancer cells possibly through suppression of osteoclastic bone- resorption in nude mice. J Immunother 2002;25 Suppl 1:52-60.
15. Cao Q, Cai W, Niu G, He L, Chen X. Multimodal- ity imaging of IL-18--binding protein-Fc therapy of experimental lung metastasis. Clin Cancer Res 2008;14(19):6137-45.
16.Mackie PS, Fisher JL, Zhou H, Choong PF. Bisphos- phonates regulate cell growth and gene expression in the UMR 106-01 clonal rat osteosarcoma cell line. Br J Cancer 2001;84(7):951-8.
17. Gao YH, Shinki T, Yuasa T, Kataoka-Enomoto H, Ko- mori T, Suda T, et al. Potential role of cbfa1, an essen- tial transcriptional factor for osteoblast differentiation, in osteoclastogenesis: regulation of mRNA expression of osteoclast differentiation factor (ODF). Biochem Biophys Res Commun 1998;252(3):697-702.
18.Hsu H, Lacey DL, Dunstan CR, Solovyev I, Colombe- ro A, Timms E, et al. Osteoprotegerin (OPG) ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 1998;93:165-76.
19.Green JR. Bisphosphonates: preclinical review. On- cologist 2004;9 Suppl 4:3-13.
20. Yamagishi S, Abe R, Inagaki Y, Nakamura K, Sugawara H, Inokuma D, et al. Minodronate, a newly developed nitrogen-containing bisphosphonate, suppresses mel- anoma growth and improves survival in nude mice by blocking vascular endothelial growth factor signaling. Am J Pathol 2004;165(6):1865-74.