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Vol. 63 No. 10: Issue 10

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Interleukin-6 secreted by oral cancer- associated fibroblast accelerated VEGF expression in tumor and stroma cells

https://doi.org/10.14715/cmb/2017.63.10.21
M. Mirkeshavarz
Department of Oral and Maxillofacial Pathology, School of Dentistry, Tehran University of Medical Sciences, Tehran, Iran
M. Ganjibakhsh
Human and Animal cell Bank, Iranian Biological Resource Center (IBRC), ACECR, Tehran, Iran
P. Aminishakib
Dental Research Center, Dentistry Research Institute, Tehran University of Medical Sciences, Tehran, Iran
P. Farzaneh
Human and Animal cell Bank, Iranian Biological Resource Center (IBRC), ACECR, Tehran, Iran
N. Mahdavi
Department of Oral and Maxillofacial Pathology, School of Dentistry, Tehran University of Medical Sciences, Tehran, Iran
F. Vakhshiteh
Human and Animal cell Bank, Iranian Biological Resource Center (IBRC), ACECR, Tehran, Iran
A. Karimi
Department of Oral and Maxillofacial Surgery, Craniomaxillofacial Research Center, Tehran University of Medical Sciences, Tehran, Iran
N. S. Gohari
Human and Animal cell Bank, Iranian Biological Resource Center (IBRC), ACECR, Tehran, Iran
F. Kamali
Tumor Bank, Cancer Institute Hospital, Tehran University of Medical Sciences, Tehran, Iran
M. J. Kharazifard
Dental Research Center, Dentistry Research Institute, Tehran University of Medical Sciences, Tehran, Iran
S. A. Shahzadeh Fazeli
Human and Animal cell Bank, Iranian Biological Resource Center (IBRC), ACECR, Tehran, Iran
A. Nasimian
Human and Animal cell Bank, Iranian Biological Resource Center (IBRC), ACECR, Tehran, Iran

Corresponding Author(s) : A. Nasimian

Ahmad.nasimian@ibrc.ir

Cellular and Molecular Biology, Vol. 63 No. 10: Issue 10

Abstract

Oral cancer represents the sixth most common cancer type worldwide. Patients with oral cancer express high levels of IL-6 which is associated with very poor prognosis. Previous studies illustrated that IL-6 cytokine induces angiogenesis. It has also been reported that the presence of Cancer- Associated Fibroblasts (CAFs) is essential for angiogenesis. In this study, we examined the correlation between IL-6 and CAF and the role of this correlation on VEGF production. In this study, quantitative expression level of IL-6 and VEGF in CAF and Oral Cancer Cells (OCCs) examined through Real Time PCR and ELISA and western blot analysis. In addition, maintenance and retention of IL-6 and VEGF checked out in co-culture experiment of CAF and OCC cells. These experiments demonstrated that in oral cancer, CAF cell line secretes significantly more IL-6 than OCC. Also IL-6 is a factor that causes VEGF secretion in CAF cell line. CAF is the basic and the most essential source for producing IL-6 in patients with oral cancer. Secreted IL-6 is able to induce VEGF production in both CAF and OCCs. Correlation between CAF, IL-6 and VEGF could be considered as an approach for cancer therapy.

Keywords

Interleukin-6 Cancer- Associated fibroblast VEGF Oral cancer cells Normal fibroblast.
Mirkeshavarz, M., Ganjibakhsh, M., Aminishakib, P., Farzaneh, P., Mahdavi, N., Vakhshiteh, F., Karimi, A., Gohari, N. S., Kamali, F., Kharazifard, M. J., Shahzadeh Fazeli, S. A., & Nasimian, A. (2017). Interleukin-6 secreted by oral cancer- associated fibroblast accelerated VEGF expression in tumor and stroma cells. Cellular and Molecular Biology, 63(10), 131–136. https://doi.org/10.14715/cmb/2017.63.10.21
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References
  1. Li, H., Zhang, J., Chen, S.-W., Liu, L.-l., Li, L., Gao, F., Zhuang, S.-M., Wang, L.-p., Li, Y.,Song, M., Cancer-associated fibroblasts provide a suitable microenvironment for tumor development and progression in oral tongue squamous cancer. Journal of translational medicine, 2015; 13(1): 198.
  2. Hernández Guerrero, J.C., Jacinto Alemán, L.F., Jiménez Farfán Farfán, M.D., Macario Hernández, A., Hernández Flores, F.,Alcántara Vázquez, A., Prevalence trends of oral squamous cell carcinoma. Mexico City's General Hospital experience. 2013.
  3. Wang, B., Zhang, S., Yue, K.,Wang, X.-D., The recurrence and survival of oral squamous cell carcinoma: a report of 275 cases. Chin J Cancer, 2013; 32(11): 614-8.
  4. Feller, L. and Lemmer, J., Oral squamous cell carcinoma: Epidemiology, clinical presentation and treatment. 2012.
  5. Li, J., Jia, Z., Kong, J., Zhang, F., Fang, S., Li, X., Li, W., Yang, X., Luo, Y.,Lin, B., Carcinoma-associated fibroblasts lead the invasion of salivary gland adenoid cystic carcinoma cells by creating an invasive track. PloS one, 2016; 11(3): e0150247.
  6. Tang, D., Gao, J., Wang, S., Ye, N., Chong, Y., Huang, Y., Wang, J., Li, B., Yin, W.,Wang, D., Cancer-associated fibroblasts promote angiogenesis in gastric cancer through galectin-1 expression. Tumor Biology, 2016; 37(2): 1889-1899.
  7. Liang, Y., Brekken, R.A.,Hyder, S.M., Vascular endothelial growth factor induces proliferation of breast cancer cells and inhibits the anti-proliferative activity of anti-hormones. Endocrine-related cancer, 2006; 13(3): 905-919.
  8. Mćƒrgćƒritescu, C., Pirici, D., Stí®ngćƒ, A., Simionescu, C., Raica, M., Mogoantćƒ, L., Stepan, A.,Ribatti, D., VEGF expression and angiogenesis in oral squamous cell carcinoma: an immunohistochemical and morphometric study. Clinical and experimental medicine, 2010; 10(4): 209-214.
  9. Aggarwal, S., Devaraja, K., Sharma, S.C.,Das, S.N., Expression of vascular endothelial growth factor (VEGF) in patients with oral squamous cell carcinoma and its clinical significance. Clinica Chimica Acta, 2014; 436: 35-40.
  10. Gopinathan, G., Milagre, C., Pearce, O.M., Reynolds, L.E., Hodivala-Dilke, K., Leinster, D.A., Zhong, H., Hollingsworth, R.E., Thompson, R.,Whiteford, J.R., Interleukin-6 stimulates defective angiogenesis. Cancer research, 2015; 75(15): 3098-3107.
  11. Zhao, Z.F., Li, J.X., Ye, R., Wu, X., Gao, L.L.,Niu, B.L., Interleukin"‘6 as a potential molecular target in esophageal squamous cell carcinoma. Oncology letters, 2016; 11(2): 925-932.
  12. Chen, C.-J., Sung, W.-W., Lin, Y.-M., Chen, M.-K., Lee, C.-H., Lee, H., Yeh, K.-T.,Ko, J.-L., Gender difference in the prognostic role of interleukin 6 in oral squamous cell carcinoma. PLoS One, 2012; 7(11): e50104.
  13. Mihara, M., Hashizume, M., Yoshida, H., Suzuki, M.,Shiina, M., IL-6/IL-6 receptor system and its role in physiological and pathological conditions. Clinical science, 2012; 122(4): 143-159.
  14. Nikakhlagh, S., Ranjbari, N., Khorami, E.,Saki, N., Association between Serum Levels of Interleukin-6 and Stage of Laryngeal Cancer. Iranian journal of otorhinolaryngology, 2015; 27(80): 199.
  15. Wan, S., Zhao, E., Kryczek, I., Vatan, L., Sadovskaya, A., Ludema, G., Simeone, D.M., Zou, W.,Welling, T.H., Tumor-associated macrophages produce interleukin 6 and signal via STAT3 to promote expansion of human hepatocellular carcinoma stem cells. Gastroenterology, 2014; 147(6): 1393-1404.
  16. Wang, L., Miyahira, A.K., Simons, D.L., Lu, X., Chang, A.Y., Wang, C., Suni, M.A., Maino, V.C., Dirbas, F.M.,Yim, J., IL6 Signaling in Peripheral Blood T Cells Predicts Clinical Outcome in Breast Cancer. Cancer Research, 2017; 77(5): 1119-1126.
  17. Sousa, S., Brion, R., Lintunen, M., Kronqvist, P., Sandholm, J., Mönkkönen, J., Kellokumpu-Lehtinen, P.-L., Lauttia, S., Tynninen, O.,Joensuu, H., Human breast cancer cells educate macrophages toward the M2 activation status. Breast Cancer Research, 2015; 17(1): 101.
  18. Woods, K.V., Adler-Storthz, K., Clayman, G.L., Francis, G.M.,Grimm, E.A., 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 research, 1998; 58(14): 3142-3149.
  19. Tang, C.-H., Chuang, J.-Y., Fong, Y.-C., Maa, M.-C., Way, T.-D.,Hung, C.-H., Bone-derived SDF-1 stimulates IL-6 release via CXCR4, ERK and NF-κB pathways and promotes osteoclastogenesis in human oral cancer cells. Carcinogenesis, 2008; 29(8): 1483-1492.
  20. Nagasaki, T., Hara, M., Nakanishi, H., Takahashi, H., Sato, M.,Takeyama, H., Interleukin-6 released by colon cancer-associated fibroblasts is critical for tumour angiogenesis: anti-interleukin-6 receptor antibody suppressed angiogenesis and inhibited tumour–stroma interaction. British journal of cancer, 2014; 110(2): 469-478.
  21. Liu, S., Ginestier, C., Ou, S.J., Clouthier, S.G., Patel, S.H., Monville, F., Korkaya, H., Heath, A., Dutcher, J.,Kleer, C.G., Breast cancer stem cells are regulated by mesenchymal stem cells through cytokine networks. Cancer research, 2011; 71(2): 614-624.
  22. Nilsson, M.B., Langley, R.R.,Fidler, I.J., Interleukin-6, secreted by human ovarian carcinoma cells, is a potent proangiogenic cytokine. Cancer research, 2005; 65(23): 10794-10800.
  23. Shintani, Y., Fujiwara, A., Kimura, T., Kawamura, T., Funaki, S., Minami, M.,Okumura, M., IL-6 Secreted from Cancer-Associated Fibroblasts Mediates Chemoresistance in NSCLC by Increasing Epithelial-Mesenchymal Transition Signaling. Journal of Thoracic Oncology, 2016; 11(9): 1482-1492.
  24. Hugo, H.J., Lebret, S., Tomaskovic-Crook, E., Ahmed, N., Blick, T., Newgreen, D.F., Thompson, E.W.,Ackland, M.L., Contribution of fibroblast and mast cell (afferent) and tumor (efferent) IL-6 effects within the tumor microenvironment. Cancer microenvironment, 2012; 5(1): 83-93.
  25. Hwang, Y.S., Lee, S.K., Park, K.-K.,Chung, W.-Y., Secretion of IL-6 and IL-8 from lysophosphatidic acid-stimulated oral squamous cell carcinoma promotes osteoclastogenesis and bone resorption. Oral oncology, 2012; 48(1): 40-48.
  26. Bernabé, D.G., Tamae, A.C., Biasoli, í‰.R.,Oliveira, S.H., Stress hormones increase cell proliferation and regulates interleukin-6 secretion in human oral squamous cell carcinoma cells. Brain, behavior, and immunity, 2011; 25(3): 574-583.
  27. Hanahan, D. and Weinberg, R.A., Hallmarks of cancer: the next generation. cell, 2011; 144(5): 646-674.
  28. Sakurai, T. and Kudo, M., Signaling pathways governing tumor angiogenesis. Oncology, 2011; 81(Suppl. 1): 24-29.
  29. Coward, J., Kulbe, H., Chakravarty, P., Leader, D., Vassileva, V., Leinster, D.A., Thompson, R., Schioppa, T., Nemeth, J.,Vermeulen, J., Interleukin-6 as a therapeutic target in human ovarian cancer. Clinical Cancer Research, 2011; 17(18): 6083-6096.
  30. Hsu, C.P., Chen, Y.L., Huang, C.C., Chou, C.C., Liu, C.L., Hung, C.H., Kao, T.Y.,Chung, Y.C., Anti"interleukin"6 receptor antibody inhibits the progression in human colon carcinoma cells. European journal of clinical investigation, 2011; 41(3): 277-284.
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