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IL-6 Plays Crucial Roles in Sporadic Colorectal Cancer through the Cytokine Networks including CXCL7

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DOI: 10.4236/jct.2012.326112    3,701 Downloads   5,703 Views   Citations

ABSTRACT

IL-6 is a multifunctional cytokine and involved in variety of carcinogenesis. However, the association between IL-6 and sporadic colorectal cancer has not been fully explained. Here, we investigated the role of IL-6 signaling and the cytokine network in sporadic colorectal cancer. We investigated the serum IL-6 levels in patients with sporadic colorectal adenoma, cancer patients, and normal controls. In addition, the expressions of IL-6, gp130, and the IL-6 receptor subunit were investigated in biopsy specimens collected from these subjects. Furthermore, the expressions of CXCL7 and CXCR2, a chemokine and its receptor involved in IL-6 production, were also investigated. We observed an elevated level of serum IL-6 in colorectal cancer patients and an increased expression of IL-6 in colorectal cancer tissues, compared with the levels in a control group and in patients with adenoma. The phosphorylation of gp130 was also increased in the colorectal cancer tissues, compared with that in control and adenoma tissues. The expressions of CXCL7 and CXCR2 in the colorectal cancer tissues were also higher than those in control and adenoma tissues. IL-6 signaling is involved in sporadic colorectal cancer. In addition, the increased expressions of CXCL7 and CXCR2 might, in turn, increase the expression of IL-6 in colorectal cancer. Further studies are required to elucidate the function of the IL-6 signaling and the cytokine network in sporadic colorectal cancer.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

T. Uchiyama, H. Takahashi, H. Endo, E. Sakai, K. Hosono, Y. Nagashima and A. Nakajima, "IL-6 Plays Crucial Roles in Sporadic Colorectal Cancer through the Cytokine Networks including CXCL7," Journal of Cancer Therapy, Vol. 3 No. 6A, 2012, pp. 874-879. doi: 10.4236/jct.2012.326112.

References

[1] A. Jemal, R. Siegel, J. Xu and E. Ward, “Cancer statistics, 2010,” CA: A Cancer Journal for Clinicians, Vol. 60, No. 5, 2010, pp. 277-300. doi.org/10.3322/caac.20073
[2] E. Langholz, P. Munkholm, M. Davidsen and V. Binder, “Colorectal Cancer Risk and Mortality in Patients with Ulcerative Colitis,” Gastroenterology, Vol. 103, No. 5, 1992, pp. 1444-1451.
[3] W. Holtkamp, T. Stollberg and H. E. Reis, “Serum Interleukin-6 Is Related to Disease Activity but Not Disease Specificity in Inflammatory Bowel Disease,” Journal of Clinical Gastroenterology, Vol. 20, No. 2, 1995, pp. 123-126. doi:10.1097/00004836-199503000-00010
[4] C. Niederau, F. Backmerhoff, B. Schumacher and C. Niederau, “Inflammatory Mediators and Acute Phase Proteins in Patients with Crohn’s Disease and Ulcerative Colitis,” Hepatogastroenterology, Vol. 44, No. 13, 1997, pp. 90-107.
[5] T. Kishimoto, “Interleukin-6: From Basic Science to Medicine—40 Years in Immunology,” Annual Review of Immunology, Vol. 23, 2005, pp. 1-21. doi:10.1146/annurev.immunol.23.021704.115806
[6] S. Liu, C. Ginestier and S.J. Ou, “Breast Cancer Stem Cells Are Regulated by Mesenchymal Stem Cells through Cytokine Networks,” Cancer Reserch, Vol. 71, No. 6, 2011, pp. 614-624. doi:10.1158/0008-5472.CAN-10-0538
[7] Z. Tang, M. Yu, F. Miller, R. S. Berk, G. Tromp and M. A. Kosir, “Increased Invasion through Basement Membrane by CXCL7-Transfected Breast Cells,” The American Journal of Surgery, Vol. 196, No. 5, 2008, pp. 690-696. doi:10.1016/j.amjsurg.2008.08.001
[8] T. Taga and T. Kishimoto, “Gp130 and the Interleukin-6 Family of Cytokines”, Annual Review of Immunology, Vol. 15, 1997, pp. 797-815. doi:10.1146/annurev.immunol.15.1.797
[9] Z. Zhong, Z.Wen and J. E. Jr. Darnell, “Stat3: A STAT Family Member Activated by Tyrosine Phosphorylation in Response to Epidermal Growth Factor and Inter- leukin-6,” Science, Vol. 264, No. 5155, 1994, pp. 95-98. doi:10.1126/science.8140422
[10] T. Kordula, M. Bugno, J. Goldstein, and J. Travis, “Activation of Signal Transducer and Activator of Transcription-3 (Stat3) Expression by Interferon-Gamma and Interleukin-6 in Hepatoma Cells,” Biochemical and Biophysical Research Communications, Vol. 216, No. 3, 1995, pp. 999-1005. doi.org/10.1006/bbrc.1995.2719
[11] T. Kusaba, T. Nakayama, K. Yamazumi, Y. Yakata, A. Yosizaki, T. Nagayasu and I. Sekine, “Expression of p-STAT3 in Human Colorectal Adenocarcinoma and Adenoma; Correlation with Clinicopathological Factors,” Journal of Clinical Pathology, Vol. 58, No. 8, 2005, pp. 833-838. doi:10.1136/jcp.2004.023416
[12] J. K. Park, R. Hong, K. J. Kim, T. B. Lee and S. C. Lim, “Significance of p-STAT3 Expression in Human Colorectal Adenocarcinoma,” Oncology Reports, Vol. 20, No. 3, 2008, pp. 597-604. doi:10.3892/or00000047
[13] X. T. Ma, S. Wang, Y. J. Ye, R. Y. Du, Z. R. Cui and M. Somsouk, “Constitutive Activation of Stat3 Signaling Pathway in Human Colorectal Carcinoma,” World Journal of Gastroenterology, Vol. 10, No. 11, 2004, pp. 1569-1573.
[14] F.M. Corvinus, C. Orth, R. Moriggl, S. A. Tsareva, S. Wagner, E. B. Pfitzner, D. Baus, R. Kaufmann, L. A. Huber, K. Zatloukal, H. Beug, P. Ohlschlager, A. Schütz, K. J. Halbhuber and K. Friedrich, “Persistent STAT3 Activation in Colon Cancer Is Associated with Enhanced Cell Proliferation and Tumor Growth,” Neoplasia, Vol. 7, No. 6, 2005, PP. 545-555. doi:10.1593/neo.04571
[15] G. Kalwitz, M. Endres, K. Neumann, K. Skriner, J. Ringe, O. Sezer, M. Sittinger, T. Haupl and C. Kaps, “Gene Expression Profile of Adult Human Bone Marrow-Derived Mesenchymal Stem Cells Stimulated by the Chemokine CXCL7,” The International Journal of Biochemistry & Cell Biology, Vol. 41, No. 3, 2009, 649-658. doi.org/10.1016/j.biocel.2008.07.011

  
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