سطح سرمی عوامل محرک کلونی گرانولوسیتی، ماکروفاژی و گرانولوسیتی- ماکروفاژی در خون محیطی بیماران مبتلا به تومور پستان

رزمخواه, محبوبه; کریم زاده, پریسا; اقبالی, فاطمه; رضایی فرد, سمیه; فقیه, زهرا

نوع مقاله : مقاله پژوهشی

نویسندگان

¹ مرکز تحقیقات سرطان، دانشکده پزشکی، دانشگاه علوم پزشکی شیراز، شیراز، ایران

² مرکز تحقیقات سرطان، دانشکده پزشکی، دانشگاه علوم پزشکی شیراز، شیراز، ایران،

³ بیمارستان نمازی، دانشکده پزشکی، دانشگاه علوم پزشکی شیراز، شیراز، ایران،

چکیده

زمینه و هدف: عوامل محرک کلونیگلیکوپروتئین‌هایی هستند که تکثیر و تمایز سلول‌های پیش‌ساز خونساز را در مغز استخوان تحریک میکنند. اما مطالعات متعدد نشان داده اند این فاکتورها می توانند سبب تحریک تکثیر سلولهای غیر خونساز، از جمله سلول‌های سرطانی نیز شوند. از این رو در این مطالعه عوامل محرک کلونی-ماکروفاژی (M-CSF)، ماکروفاژی-گرانولوسیتی (GM-CSF) و گرانولوسیتی (G-CSF) در سرم بیماران مبتلا به تومور پستان وارتباط آنها با پارامترهای پاتولوژیکی و پاراکلینیکال بیماری مورد بررسی قرار گرفت.
مواد و روش‌ ها: 62 بیمار مبتلا به سرطان پستان که هیچ درمانی دریافت نکرده بودند و 54 زن سالم که از لحاظ سنی با گروه بیمار همخوانی داشتند بعنوان گروه کنترل وارد مطالعه شدند. از هر دو گروه پس از اخذ رضایت اگاهانه 5 سی‌سی خون محیطی گرفته شد و سرم آنها جدا گردید. سطح سرمی سایتوکاین‌های مورد بررسی با روش cytokine-bead array اندازه‌گیری گردید. داده‌ها با نرم افزار SPSS18 و سطح معنی‌داری 05/0 مورد بررسی قرار گرفت.
یافته ‌ها: میانگین سطح سرمی فاکتورهای رشد G-CSF، M-CSF و GM-CSF در بیماران مبتلا به سرطان پستان بیماران به ترتیب 16/13±18/14، 62/5±11/6 و 22/83±48/63 pg/ml محاسبه شد. هرچند که آنالیز آماری تفاوت معناداری بین سطح سرمی این فاکتورهای رشد در دو گروه بیمار و گروه کنترل نشان نداد (P>0.05)، اما بررسیهای بیشتر نشان داد که با افزایش مرحله بیماری از I به III سطح سرمی GM-CSF بطور معناداری کاهش می‌یابد (P=0.016).
نتیجه‌ ‌گیری: در مجموع نتایج این مطالعه حاکی از نقش آنتی‌تومورژنیک GM-CSF در سرطان پستان بود. هرچند که تایید این نتایج نیازمند انجام مطالعات کامل‌تر با حجم نمونه بیشتر است.

کلیدواژه‌ها

موضوعات

ایمنی شناسی و بیوشیمی

عنوان مقاله [English]

Serum level of colony stimulating factors, Granulocyte, Monocyte and Granulocyte-Monocyte, in peripheral blood of patients with breast cancer

نویسندگان [English]

Mahboobeh Razmkhah ¹
Parisa Karimzadeh ²
Fatemeh Eghbali ³
Somayeh Rezaeifard ²
Zahra Faghih ¹

¹ Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

² Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

³ School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

چکیده [English]

Background: Colony stimulating factors (CSFs) are a group of diverse glycoproteins which induce and regulate proliferation and differentiation of hematogenic progenitors in the bone marrow. However, increasing evidence also shows that these factors can also affect and provoke proliferation of non-hematopoietic cells including tumor cells. Therefore, we assessed Granulocyte (G-CSF), Monocyte (M-CSF) and Granulocyte-Monocyte (GM-CSF) colony stimulating factors the serum of breast cancer (BC) and their association with pathological and paraclinical factors of the disease.
Materials and Methods: Sixty-two untreated patients with BC as well as 54 age-sex matched controls without any history of cancer and autoimmunity in themselves and their first degree relatives were enrolled. After assigning a consent form, 5 milliliters of peripheral blood were obtained and their serums were separated. The levels of growth factors were then checked by cytokine bead array methods. The data were analyzed by SPSS18 and P-values less than 0.05 were considered as significant.
Results: The mean expression of G-CSF, M-CSF and GM-CSF was measured to be 14.18 ± 13.61, 6.11 ± 5.62 and 63.48 ±83.22 in the serum of BC patients, respectively. However, there was no significant difference between patients and controls (P>0.05), further analysis revealed that with increase in the stage of disease from I to III, the serum level of GM-CSF significantly elevated (P=0.016).
Conclusion: The results collectively suggest an anti-tumorigenic role for GM-CSF in breast cancer, however, it needs to be confirmed in a more comprehensive studies with more sample size.

کلیدواژه‌ها [English]

Breast Cancer
Peripheral blood
G-CSF
M-CSF
GM-CSF

مراجع

[1]. Wang M, Zhao J, Zhang L, Wei F, Lian Y, Wu Y, et al. Role of tumor microenvironment in tumorigenesis. Journal of Cancer. 2017;8(5):761-73.

[2].Hamilton JA, Achuthan A. Colony stimulating factors and myeloid cell biology in health and disease. Trends in immunology. 2013;34(2):81-9.

[3]. Metcalf D. Hematopoietic cytokines. Blood. 2008;111(2):485-91.

[4]. Zhao CL, Zhang GP, Xiao ZZ, Ma ZK, Lei CP, Song SY, et al. Recombinant human granulocyte colony-stimulating factor promotes preinvasive and invasive estrogenreceptor-positive tumor development in MMTV-erbB2 mice. Journal of breast cancer. 2015;18(2):126-33.

[5]. Gutschalk CM, Herold-Mende CC, Fusenig NE, Mueller MM. Granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor promote malignant growth of cells from head and neck squamous cell carcinomas in vivo. Cancer research. 2006;66(16):8026-36.

[6]. Ohmi C, Matsuyama H, Tei Y, Yoshihiro S, Shimabukuro T, Ohmoto Y, et al. Granulocyte colony-stimulating factor may promote proliferation of human bladder cancer cells mediated by basic fibroblast growth factor. Scandinavian journal of urology and nephrology. 2003;37(4):286-91.

[7]. Matsuoka Y, Arai G, Okada Y, Aida J. Prostate cancer-producing granulocyte colony-stimulating factor. Urologia internationalis. 2009;82(1):113-5.

[8]. Fukutomi T, Kohno M, Izumi Y, Watanabe M, Hayashi Y, Nomori H. Pulmonary pleomorphic carcinoma producing granulocyte–macrophage colony-stimulating factor: report of a case. Surgery today. 2012;42(3):288-91.

[9]. Demirci U, Coskun U, Sancak B, Ozturk B, Bahar B, Benekli M, et al. Serum granulocyte macrophage-colony stimulating factor: a tumor marker in colorectal carcinoma. Asian Pac J Cancer Prev. 2009;10(6):1021-4.

[10]. Mroczko B, Szmitkowski M, Okulczyk B. Hematopoietic growth factors in colorectal cancer patients. Clinical chemistry and laboratory medicine. 2003;41(5):646-51.

[11]. Mroczko B, Szmitkowski M, Wereszczyńska-Siemiątkowska U, Okulczyk B, Kędra B. Pretreatment serum levels of hematopoietic cytokines in patients with colorectal adenomas and cancer. International journal of colorectal disease. 2007;22(1):33-8.

[12]. Ławicki S, Będkowska GE, Gacuta-Szumarska E, Szmitkowski M. Hematopoietic cytokines as tumor markers in gynecological malignancies: a multivariate analysis with ROC curve in endometrial cancer patients. Growth Factors. 2012;30(1):29-36.

[13]. Ławicki S, Bedkowska G, Gacuta-Szumarska E, Czygier M, Szmitkowski M. The plasma levels and diagnostic utility of selected hematopoietic growth factors in endometrial cancer patients and with myoma uteri. Polski merkuriusz lekarski: organ Polskiego Towarzystwa Lekarskiego. 2010;28(167):354-8.

[14]. Metcalf D. The colony-stimulating factors and cancer. Cancer immunology research. 2013;1(6):351-6.

[15]. Ushach I, Zlotnik A. Biological role of granulocyte macrophage colony‐stimulating factor (GM‐CSF) and macrophage colony‐stimulating factor (M‐CSF) on cells of the myeloid lineage. Journal of leukocyte biology. 2016;100(3):481-9.

[16]. Hong IS. Stimulatory versus suppressive effects of GM-CSF on tumor progression in multiple cancer types. Experimental & molecular medicine. 2016;48(7):e242.

[17]. Natori T, Sata M, Washida M, Hirata Y, Nagai R, Makuuchi M. G-CSF stimulates angiogenesis and promotes tumor growth: potential contribution of bone marrow-derived endothelial progenitor cells. Biochemical and biophysical research communications. 2002;297(4):1058-61.

[18]. Aliper AM, Frieden‐Korovkina VP, Buzdin A, Roumiantsev SA, Zhavoronkov A. A role for G‐CSF and GM‐CSF in nonmyeloid cancers. Cancer medicine. 2014;3(4):737-46.

[19]. Fleetwood AJ, Cook AD, Hamilton JA. Functions of granulocyte-macrophage colony-stimulating factor. Critical reviews in immunology. 2005;25(5):405-28.

[20]. Ushach I, Zlotnik A. Biological role of granulocyte macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF) on cells of the myeloid lineage. Journal of leukocyte biology. 2016;100(3):481-9.

[2]1. Takahashi G, Andrews D. 3d., Lilly MB, Singer JW, Alderson MR. Effect of granulocyte-macrophage colony-stimulating factor and interleukin-3 on interleukin-8 production by human neutrophils and monocytes Blood. 1993;81:357.

[22]. Eubank TD, Roberts RD, Khan M, Curry JM, Nuovo GJ, Kuppusamy P, et al. Granulocyte macrophage colony-stimulating factor inhibits breast cancer growth and metastasis by invoking an anti-angiogenic program in tumor-educated macrophages. Cancer research. 2009;69(5):2133-40.

[23]. Chaubey N, Ghosh SS. Overexpression of granulocyte macrophage colony stimulating factor in breast cancer cells leads towards drug sensitization. Applied biochemistry and biotechnology. 2015;175(4):1948-59.

[24]. Hamilton JA. GM-CSF as a target in inflammatory/autoimmune disease: current evidence and future therapeutic potential. Expert review of clinical immunology. 2015;11(4):457-65.

[25]. Sapi E. The role of CSF-1 in normal physiology of mammary gland and breast cancer: an update. Experimental biology and medicine (Maywood, NJ). 2004;229(1):1-11.

[26]. Eubank TD, Galloway M, Montague CM, Waldman WJ, Marsh CB. M-CSF induces vascular endothelial growth factor production and angiogenic activity from human monocytes. The Journal of Immunology. 2003;171(5):2637-43.

[27]. Hagemann T, Robinson SC, Schulz M, Trümper L, Balkwill FR, Binder C. Enhanced invasiveness of breast cancer cell lines upon co-cultivation with macrophages is due to TNF-α dependent up-regulation of matrix metalloproteases. Carcinogenesis. 2004;25(8):1543-9.

[28]. Asschert J, Vellenga E, Hollema H, Van Der Zee A, De Vries E. Expression of macrophage colony-stimulating factor (M-CSF), interleukin-6 (il-6), interleukin-lβ (IL-Iβ), interleukin-11 (IL-11) and tumour necrosis factor-α (TNF-α) in p53-characterised human ovarian carcinomas. European Journal of Cancer. 1997;33(13):2246-51.

[29]. Yee LD, Liu L. The constitutive production of colony stimulating factor 1 by invasive human breast cancer cells. Anticancer research. 2000;20(6B):4379-83.

[30]. Richardsen E, Uglehus RD, Johnsen SH, Busund LT. Macrophage-colony stimulating factor (CSF1) predicts breast cancer progression and mortality. Anticancer research. 2015;35(2):865-74.

[31]. Sapi E. The role of CSF-1 in normal physiology of mammary gland and breast cancer: an update. Experimental Biology and Medicine. 2004;229(1):1-11.

[32]. LinEY, Nguyen AV, Russell RG, Pollard JW. Colony-stimulating factor 1 promotes progression of mammary tumors to malignancy. Journal of Experimental Medicine. 2001;193(6):727-40.

[33]. McDermott RS, Deneux L, Mosseri V, Védrenne J, Clough K, Fourquet A, et al.Circulating macrophage colony stimulating factor as a marker of tumour progression. European cytokine network. 2002;13(1):121-7.

[34]. Scholl SM, Lidereau R, De La Rochefordière A, Le-Nir CC-S, Mosseri V, Noguès C, et al. Circulating levels of the macrophage colony stimulating factor CSF-1 in primary and metastatic breast cancer patients. A pilot study. Breast cancer research and treatment. 1996;39(3):275-83.

[35]. Ławicki S, Szmitkowski M, Wojtukiewicz M. The pretreatment plasma level and diagnostic utilityof M-CSF in benign breast tumor and breast cancer patients. Clinica chimica acta. 2006;371(1):112-6.

[36]. Lammel V, Stoeckle C, Padberg B, Zweifel R, Kienle DL, Reinhart WH, et al. Hypereosinophilia driven by GM-CSF in large-cell carcinoma of the lung. Lung Cancer. 2012;76(3):493-5.

[37]. Bahar B, Cayci B, Coskun U, Buyukberber S, Benekli M, Yildiz R. Granulocyte colony stimulating factor (G-CSF) and macrophage colony stimulating factor (M-CSF) as potential tumor markers in non-small cell lung cancer diagnosis. Asian Pacific J Cancer Prev. 2010;11:709-12.

[38]. Ławicki S, Czygier M, Wojtukiewicz M, Szmitkowski M. The plasma levels and diagnostic utility of granulocyte-colony stimulating factor (G-CSF) and granulocyte-macrophage-colony stimulating factor (GM-CSF) in patients with I and II stage of breast cancer. Przeglad lekarski. 2009;66(7):365-9.

[39]. Bordbar E, Malekzadeh M, Ardekani MT, Doroudchi M, Ghaderi A. Serum levels of G-CSF and IL-7 in Iranian breast cancer patients. Asian Pacific journal of cancer prevention : APJCP. 2012;13(10):5307-12.

[40]. Pei X-H, Nakanishi Y, Takayama K, Yatsunami J, Bai F, Kawasaki M, et al. Granulocyte-colony stimulating factor promotes invasion by human lung cancer cell lines in vitro. Clinical & experimental metastasis. 1996;14(4):351-7.

[41]. Mroczko B, Wereszczyñska-Siemiątkowska U, Groblewska M, Lukaszewicz M, Szmitkowski M, Gryko M, et al. The diagnostic value of hematopoietic cytokines measurement in the sera of gastric cancer and gastric ulcer patients. Clinica Chimica Acta. 2006;374(1):165-7.

مجله دانشگاه علوم پزشکی سبزوار

سطح سرمی عوامل محرک کلونی گرانولوسیتی، ماکروفاژی و گرانولوسیتی- ماکروفاژی در خون محیطی بیماران مبتلا به تومور پستان

مراجع

مراجع

دوره 25، شماره 6
بهمن و اسفند 1397
صفحه 809-817

سطح سرمی عوامل محرک کلونی گرانولوسیتی، ماکروفاژی و گرانولوسیتی- ماکروفاژی در خون محیطی بیماران مبتلا به تومور پستان

مراجع

مراجع

دوره 25، شماره 6بهمن و اسفند 1397صفحه 809-817

دوره 25، شماره 6
بهمن و اسفند 1397
صفحه 809-817