نوع مقاله: مقاله کوتاه

نویسندگان

1 دکتری، گروه ایمنی شناسی، دانشکده پزشکی، دانشگاه علوم پزشکی شیراز، شیراز، ایران

2 کارشناسی ارشد، مرکز تحقیقات سرطان، دانشگاه علوم پزشکی شیراز، شیراز، ایران

3 مرکز تحقیقات سرطان، دانشگاه علوم پزشکی شیراز، شیراز، ایران

چکیده

سرطان های استخوان اولیه از نوع استئوسارکوما شایعترین اختلالات بدخیمی در دستگاه اسکلتی-عضلانی انسان می باشند. فاکتورهای خطر متعددی از جمله واکنش های التهابی و فاکتورهای ایمونولوژیک در این بیماری معرفی شده اند که از بین آنها میتوان به سایتوکاین ها اشاره کرد. هدف از این مطالعه بررسی میزان سطح سرمی اینترلوکین 7 (IL-7) به عنوان یک سایتوکاین که در مغزاستخوان حضور دارد، در بیماران مبتلا به استئوسارکوما و مقایسه آن با افراد سالم است. در این مطالعه، نمونه های سرمی 28 فرد مبتلا به سرطان استئوسارکوما و 47 فرد سالم بمنظور بررسی سطح سرمی IL-7 با استفاده از تکنیک الایزا مورد بررسی قرار گرفت. نتایج بدست آمده با استفاده از آزمون آماری t-test تجزیه و تحلیل شد.میانگین سطح سرمی IL-7 در بیماران مبتلا به سرطان استئوسارکوما و افراد گروه کنترل به ترتیب 03/0±1/0 و 02/0±08/0 پیکوگرم در میلی لیتر اندازه گیری شد و تفاوت معنی داری در میانگین سطح سرمی IL-7 بین دو گروه وجود نداشت (515/0=p value). علیرغم  افزایش سطح سرمی IL-7 در متاستاز سرطانهای خاص به استخوان، نتایج بدست آمده از این مطالعه نشان می دهد که سطح سرمی IL-7 در بیماران مبتلا به سرطان اولیه استخوان از نوع استئوسارکوما افزایش معنی داری نمی یابد.  این یافته از آن جهت اهمیت دارد که اینترلوکین 7 سیتوکاین بقای لنفوسیتها در مغز استخوان و سایر اندامهای لنفی می باشد و هرگونه تغییر در سطح آن می تواند منجر به تغییراتی در عملکرد سیستم ایمنی شود.
 

کلیدواژه‌ها

عنوان مقاله [English]

Investigation of Interleukin-7 Serum Levels in Patients with Osteosarcoma

نویسندگان [English]

  • Hamed Fouladseresht 1
  • Mahyar Malekzadeh 2
  • Abbas Ghaderi 1 3
  • Mehrnoosh Doroudchi 1 3

1 Ph.D., Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

2 MSc, Institute of Cancer Research, Shiraz University of Medical Sciences, Shiraz, Iran

3 Ph.D., Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

چکیده [English]

Primary bone cancers, mainly osteosarcoma, are the most common malignancies in human musculoskeletal system. Several risk factors including inflammatory and immunologic factors have been introduced in this disease of which cytokines can be named. The aim of this study was to investigate the serum levels of Interleukin-7 (IL-7), as a bone marrow inhabited cytokine, in patients with osteosarcoma compared to healthy individuals. In this study, serum samples from 28 patients with osteosarcoma and 47 healthy individuals were tested for IL-7 levels by ELISA technique. The results were analyzed using t-test. The mean level of IL-7 in patients with osteosarcoma and  that of the control group were 0.1 ± 0.03 and 0.08 ± 0.02 Pg/ml, respectively and there was no significant difference in IL-7 levels between the two groups  (P=0.515). Despite the increase in IL-7 serum levels during metastasis of several tumors to the bone, our results suggest that IL-7 serum levels do not increase in primary bone tumors. This finding is important since IL-7 production is important in the maintenance of the lymphocytes in bone marrow and other lymphoid organs and any change in its levels may cause disturbances in the immune system function.

کلیدواژه‌ها [English]

  • cancer
  • ELISA
  • Interleukin-7
  • Osteosarcoma

  1. Biermann JS, Chow W, Reed DR, Lucas D, Adkins DR, Agulnik M, et al. Bone cancer, version 2. 2017 featured updates to the NCCN guidelines. J Natl Compr Canc Netw 2017;15:155-67.
  2. Coffin C, Fletcher J, Fletcher C, Unni
    K, Mertens F. World Health Organization classification of tumours Pathology and genetics of tumours of soft tissue and bone.  2002. www.iarc.fr/who-bluebooks, IARC Press.
  3. Evola FR, Costarella L, Pavone V, Caff G, Cannavò L, Sessa A, et al. Biomarkers of osteosarcoma, chondrosarcoma, and Ewing sarcoma. Front Pharmacol. 2017;8:150.
  4. Geller DS, Gorlick R. Osteosarcoma: a review of diagnosis, management, and treatment strategies. Clin Adv Hematol Oncol 2010;8:705-18.
  5. Lopes-Júnior LC, Silveira DSC, Vulczak A, dos Santos JC, Veronez LC, Fisch A, et al. Emerging cytokine networks in osteosarcoma. Oncology Communications 2016;2. doi: 10.14800/oc.1167
  6. Burningham Z, Hashibe M, Spector L, Schiffman JD. The epidemiology of sarcoma. Clin Sarcoma Res 2012;2:14.
  7. Thiagarajan A, Iyer NG. Radiation-induced sarcomas of the head and neck. World J Clin Oncol 2014;5:973.
  8. Polyzoidis S, Ashkan K. DCVax®-L—
    Developed by Northwest Biotherapeutics. Hum Vaccin Immunother 2014;10:3139-45.
  9. Hanahan D, Coussens LM. Accessories to the crime: functions of cells recruited to the tumor microenvironment. Cancer cell 2012;21:309-22.
  10. Savitskaya YA, Rico-Martínez G, Linares-González LM, Delgado-Cedillo EA, Téllez-Gastelum R, Alfaro-Rodríguez AB, et al. Serum tumor markers in pediatric osteosarcoma: a summary review. Clin Sarcoma Res 2012;2:9.
  11. Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell 2010;140:883-99.
  12. Goldszmid RS, Trinchieri G. The price of immunity. Nat immunol 2012;13:932. doi: 10.1038/ni.2422.
  13. Turtle CJ, Hudecek M, Jensen MC, Riddell SR. Engineered T cells for anti-cancer therapy. Curr Opin Immunol 2012;24:633-9.
  14. Mazzucchelli R, Durum SK. Interleukin-7 receptor expression: intelligent design. Nat Rev Immunol
     2007;7:144.
  15. Rochman Y, Spolski R, Leonard WJ. New insights into the regulation of T cells by γ c family cytokines. Nat Rev Immunol 2009;9:480.
  16. Sato T, Watanabe K, Masuhara M, Hada N, Hakeda Y. Production of IL-7 is increased in ovariectomized mice, but not RANKL mRNA expression by osteoblasts/stromal cells in bone, and IL-7 enhances generation of osteoclast precursors in vitro. J Bone Miner Metab 2007;25:19-27.
  17. ElKassar N, Gress RE. An overview of IL-7 biology and its use in immunotherapy. J Immunotoxicol 2010;7:1-7.
  18. Al-Rawi M, Mansel R, Jiang WG. Interleukin-7 (IL-7) and IL-7 receptor (IL-7R) signalling complex in human solid tumours. Histol and histopathol 2003;18:911-23.
  19. Roato I, Grano M, Brunetti G, Colucci S, Mussa A, Bertetto O, et al. Mechanisms of spontaneous osteoclastogenesis in cancer with bone involvement. FASEB J 2005;19:228-30.
  20. Kim J-H, Sim JH, Lee S, Seol MA, Ye
    S-K, Shin HM, et al. Interleukin-7 induces osteoclast formation via STAT5, independent of receptor activator of NF-kappaB ligand. Front Immunol 2017;8:1376.
  21. Lee SK, Kalinowski JF, Jacquin C, Adams DJ, Gronowicz G, Lorenzo JA. Interleukin‐7 influences osteoclast function in vivo but is not a critical factor in ovariectomy‐induced bone loss. J Bone Miner Res 2006;21:695-702.
  22. Amin MB, Greene FL, Edge SB, Compton CC, Gershenwald JE, Brookland RK, et al. The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population‐based to a more “personalized” approach to cancer staging. CA Cancer J Clin 2017;67:93-9.
  23. Mojtahedi Z, Khademi B, Erfani N, Taregh Y, Rafati Z, Malekzadeh M, et al. Serum levels of interleukin-7 and interleukin-8 in head and neck squamous cell carcinoma. Indian J Cancer 2014;51:227.
  24. Mackay I, Rosen FS, Delves P, Roitt I. The immune system. N Engl J Med 2000;343:37-49.
  25. Xiao H, Chen L, Luo G, Son H, Prectoni JH, Zheng W. Effect of the cytokine levels in serum on osteosarcoma. Tumor Biol 2014;35:1023-8.
  26. Roato I, Gorassini E, Brunetti G, Grano M, Ciuffreda L, Mussa A, et al. IL‐7 Modulates Osteoclastogenesis in Patients Affected by Solid Tumors. Ann N Y Acad Sci 2007;1117:377-84.
  27. Paleri V, Pulimood A, Davies G, Birchall M. Interleukins 7 and 12 are expressed in head and neck squamous cancer. Clin Otolaryngol Allied Sci 2001;26:302-6.
  28. Linkov F, Lisovich A, Yurkovetsky Z, Marrangoni A, Velikokhatnaya L, Nolen B, et al. Early detection of head and neck cancer: development of a novel screening tool using multiplexed immunobead-based biomarker profiling. Cancer Epidemiol Biomarkers Prev 2007;16:102-7.
  29. Toraldo G, Roggia C, Qian W-P, Pacifici R, Weitzmann MN. IL-7 induces bone loss in vivo by induction of receptor activator of nuclear factor κB ligand and tumor necrosis factor α from T cells. Proc Natl Acad Sci U S A 2003;100:125-30.
  30. Weitzmann MN, Cenci S, Rifas L, Brown C, Pacifici R. Interleukin-7 stimulates osteoclast formation by up-regulating the T-cell production of soluble osteoclastogenic cytokines. Blood 2000;96:1873-8. 
  31. Lee S-K, Kalinowski JF, Jastrzebski SL, Puddington L, Lorenzo JA. Interleukin-7 is a direct inhibitor of in vitro osteoclastogenesis. Endocrinology 2003;144:3524-31.
  32. Ardekani MTF, Malekzadeh M, Hosseini SV, Bordbar E, Doroudchi M, Ghaderi A. Evaluation of pre-treatment serum levels of IL-7 and GM-CSF in colorectal cancer patients. Int J Mol Cell Med 2014;3:27.
  33. Bordbar E, Malekzadeh M, Ardekani MTF, Doroudchi M, Ghaderi A. Serum levels of G-CSF and IL-7 in Iranian breast cancer patients. Asian Pac J Cancer Prev 2012;13:5307-12.
  34. Lambeck AJ, Crijns AP, Leffers N,  Sluiter WJ, Klaske A, Braid M, et al. Serum cytokine profiling as a diagnostic and prognostic tool in ovarian cancer: a potential role for interleukin 7. Clin Cancer Res 2007;13:2385-91.
  35. Mengus C, Le Magnen C, Trella E,
    Yousef K, Bubendorf L, Provenzano M, et al. Elevated levels of circulating IL-7 and IL-15 in patients with early stage prostate cancer. J Transl Med 2011;9:162. 1.