Yıl 2019, Cilt 4 , Sayı 3, Sayfalar 132 - 137 2019-12-01

The effects of mesenchymal stem cells on the IDO, HLA-G and PD-L1 expression of breast tumor cells MDA-MB-231 and MCF-7
Mezenkimal kök hücrelerin, meme tümörü hücreleri MDA-MB-231 ve MCF-7’nin IDO, HLA-G ve PD-L1 ifadeleri üzerine etkileri

Rabia Bilge Özgül Özdemir [1] , Alper Tunga Özdemir [2] , Cengiz Kırmaz [3] , Mehmet İbrahim Tuğlu [4] , Özgür Şenol [5] , Cenk Serhan Özverel [6] , Afig Berdeli [7]


Aim: Mesenchymal stem cells (MSCs) are strong immunomodulatory cells and a component of the tumor microenvironment. In this study, we aimed to investigate the effects of MSCs derived from adipose tissue on the expressions of immune evasive molecules indoleamine 2,3-dioxygenase (IDO), human leukocyte antigen G (HLA-G) and programmed death-ligand 1 (PD-L1) of breast tumor cell lines MDA-MB-231 and MCF-7. 

Methods: For this purpose, MSCs, MDA-MB-231 and MCF-7 cells were cultured with increased doses of interferon gamma (IFN-g). In another plate, tumor cells were cultured in transwell inserts using the same IFN-g stimulation to evaluate the effect of MSCs. At the end of the culture period, the HLA-G and PD-L1 expression was detected by flow cytometry, and IDO expression by the Luminex method.

Results: We found that in low-dose IFN-g stimulation (10 ng/mL), MSCs led to a significant increase in the HLA-G and PD-L1 expression of MCF-7 cells. On the contrary, at a high dose of IFN-g (50 ng/mL), their expression significantly decreased in both tumor cells. In addition, we observed that the IDO expression of MDA-MB-231 cells was significantly increased in the presence of MSCs, but MCF-7 cells were not affected.

Conclusion: In conclusion, for MDA-MB-231 cells, MSCs may play a protective role because they reduce the expression of HLA-G and PD-L1 that are involved in the suppression of cytotoxic cells and exhaustion of T cells. On the other hand, MSCs may be an important source of high IDO levels, and therefore may negatively affect the antitumor immune response. However, our data should be supported by further studies.

Amaç: Mezenkimal kök hücreler (MKH) güçlü immünomodülatör hücreleridir ve ayrıca tümör mikroçevresinin bir bileşenidir. Bu çalışmada meme tümör hücre hatları MDA-MB-231 ve MCF-7’nin immün evazif moleküller olan Indoleamine 2,3-dioxygenase (IDO), Human Leukocyte Antigen G (HLA-G) and Programmed Death-Ligand 1 (PD-L1) ifadelerine yağ dokusu kökenli mezenkimal kök hücrelerin etkilerini araştırmayı amaçladık.

Yöntemler: Bu amaçla MKH, MDA-MB-231 ve MCF-7 hücrelerini artan dozlarda interferon gama (IFN-g) ile kültüre edildi. Başka bir kültür kabında MKH’ler ile tümör hücreleri trans-well insertler ve aynı IFN-g uyarımı ile kültür edildi. Kültür süresinin bitiminde HLA-G ve PD-L1 ifadeleri flow-sitmotetri yöntemi ile IDO ifadeleri Luminex yöntemi ile analiz edildi.

Bulgular: Düşük dozlu IFN-g uyarımında (10 ng/mL), MSC'lerin MCF-7 hücrelerinin HLA-G ve PD-L1 ekspresyonunda önemli bir artışa yol açtığını bulduk. Aksine, yüksek doz IFN-g ile (50 ng/mL) bu ifadelerin her iki tümör hücresinde de önemli ölçüde azaldığını gördük. Ek olarak, MDA-MB-231 hücrelerinin IDO ekspresyonunun MSC'lerin varlığında anlamlı şekilde arttığını, ancak MCF-7 hücrelerinin etkilenmediği gördük.

Sonuç: Sonuç olarak, MDA-MB-231 hücreleri için MSC'ler, sitotoksik hücrelerin baskılanmasında ve T hücrelerinin tükenmesinde önemli bir rol oynayan HLA-G ve PD-L1 ekspresyonunu azalttığı için koruyucu bir rol oynayabilir. Öte yandan, MSC'ler yüksek IDO seviyeleri için önemli bir kaynak olabilir ve bu nedenle anti-tümör immün yanıtı olumsuz yönde etkileyebilir. Bununla birlikte, verilerimiz diğer çalışmalarla desteklenmelidir.

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Birincil Dil en
Konular Tıp
Bölüm Orjinal Makale
Yazarlar

Orcid: 0000-0002-8171-3402
Yazar: Rabia Bilge Özgül Özdemir
Kurum: Manisa City Hospital, Department of Allergy and Clinical Immunology, Manisa
Ülke: Turkey


Orcid: 0000-0002-7708-077X
Yazar: Alper Tunga Özdemir (Sorumlu Yazar)
Kurum: Ege University, Institute of Health Sciences, Department of Stem Cell, Izmir
Ülke: Turkey


Orcid: 0000-0001-8873-1681
Yazar: Cengiz Kırmaz
Kurum: Manisa Celal Bayar University, Medical School, Department of Internal Medicine, Division of Allergy and Clinical Immunology, Manisa
Ülke: Turkey


Orcid: 0000-0002-0569-8415
Yazar: Mehmet İbrahim Tuğlu
Kurum: Manisa Celal Bayar University, Medical School, Department of Histology and Embryology, Manisa
Ülke: Turkey


Orcid: 0000-0002-1062-3290
Yazar: Özgür Şenol
Kurum: Ege University, Department of Biotechnology, İzmir
Ülke: Turkey


Orcid: 0000-0001-9932-4774
Yazar: Cenk Serhan Özverel
Kurum: Ege University, Department of Bioengineering, İzmir
Ülke: Turkey


Orcid: 0000-0001-5627-6100
Yazar: Afig Berdeli
Kurum: Ege University, Institute of Health Sciences, Department of Stem Cell, Izmir
Ülke: Turkey


Destekleyen Kurum Manisa Celal Bayar University, Scientific Research Projects Coordination Unit
Proje Numarası 2017-224
Teşekkür We would like to thank the Dr. Ayşe Nalbantsoy for the help of the flow cytometry analyzes.
Tarihler

Yayımlanma Tarihi : 1 Aralık 2019

Bibtex @araştırma makalesi { acem601633, journal = {Archives of Clinical and Experimental Medicine}, issn = {}, eissn = {2564-6567}, address = {hırkai şerif mah. keçeci çeşmesi sok. doktorlar sitesi b blok 6/7 Fatih İstanbul Türkiye}, publisher = {Mustafa Hasbahçeci}, year = {2019}, volume = {4}, pages = {132 - 137}, doi = {10.25000/acem.601633}, title = {The effects of mesenchymal stem cells on the IDO, HLA-G and PD-L1 expression of breast tumor cells MDA-MB-231 and MCF-7}, key = {cite}, author = {Özgül Özdemir, Rabia Bilge and Özdemir, Alper Tunga and Kırmaz, Cengiz and Tuğlu, Mehmet İbrahim and Şenol, Özgür and Özverel, Cenk Serhan and Berdeli, Afig} }
APA Özgül Özdemir, R , Özdemir, A , Kırmaz, C , Tuğlu, M , Şenol, Ö , Özverel, C , Berdeli, A . (2019). The effects of mesenchymal stem cells on the IDO, HLA-G and PD-L1 expression of breast tumor cells MDA-MB-231 and MCF-7. Archives of Clinical and Experimental Medicine , 4 (3) , 132-137 . DOI: 10.25000/acem.601633
MLA Özgül Özdemir, R , Özdemir, A , Kırmaz, C , Tuğlu, M , Şenol, Ö , Özverel, C , Berdeli, A . "The effects of mesenchymal stem cells on the IDO, HLA-G and PD-L1 expression of breast tumor cells MDA-MB-231 and MCF-7". Archives of Clinical and Experimental Medicine 4 (2019 ): 132-137 <https://dergipark.org.tr/tr/pub/acem/issue/50377/601633>
Chicago Özgül Özdemir, R , Özdemir, A , Kırmaz, C , Tuğlu, M , Şenol, Ö , Özverel, C , Berdeli, A . "The effects of mesenchymal stem cells on the IDO, HLA-G and PD-L1 expression of breast tumor cells MDA-MB-231 and MCF-7". Archives of Clinical and Experimental Medicine 4 (2019 ): 132-137
RIS TY - JOUR T1 - The effects of mesenchymal stem cells on the IDO, HLA-G and PD-L1 expression of breast tumor cells MDA-MB-231 and MCF-7 AU - Rabia Bilge Özgül Özdemir , Alper Tunga Özdemir , Cengiz Kırmaz , Mehmet İbrahim Tuğlu , Özgür Şenol , Cenk Serhan Özverel , Afig Berdeli Y1 - 2019 PY - 2019 N1 - doi: 10.25000/acem.601633 DO - 10.25000/acem.601633 T2 - Archives of Clinical and Experimental Medicine JF - Journal JO - JOR SP - 132 EP - 137 VL - 4 IS - 3 SN - -2564-6567 M3 - doi: 10.25000/acem.601633 UR - https://doi.org/10.25000/acem.601633 Y2 - 2019 ER -
EndNote %0 Archives of Clinical and Experimental Medicine The effects of mesenchymal stem cells on the IDO, HLA-G and PD-L1 expression of breast tumor cells MDA-MB-231 and MCF-7 %A Rabia Bilge Özgül Özdemir , Alper Tunga Özdemir , Cengiz Kırmaz , Mehmet İbrahim Tuğlu , Özgür Şenol , Cenk Serhan Özverel , Afig Berdeli %T The effects of mesenchymal stem cells on the IDO, HLA-G and PD-L1 expression of breast tumor cells MDA-MB-231 and MCF-7 %D 2019 %J Archives of Clinical and Experimental Medicine %P -2564-6567 %V 4 %N 3 %R doi: 10.25000/acem.601633 %U 10.25000/acem.601633
ISNAD Özgül Özdemir, Rabia Bilge , Özdemir, Alper Tunga , Kırmaz, Cengiz , Tuğlu, Mehmet İbrahim , Şenol, Özgür , Özverel, Cenk Serhan , Berdeli, Afig . "The effects of mesenchymal stem cells on the IDO, HLA-G and PD-L1 expression of breast tumor cells MDA-MB-231 and MCF-7". Archives of Clinical and Experimental Medicine 4 / 3 (Aralık 2019): 132-137 . https://doi.org/10.25000/acem.601633
AMA Özgül Özdemir R , Özdemir A , Kırmaz C , Tuğlu M , Şenol Ö , Özverel C , Berdeli A . The effects of mesenchymal stem cells on the IDO, HLA-G and PD-L1 expression of breast tumor cells MDA-MB-231 and MCF-7. ACEM. 2019; 4(3): 132-137.
Vancouver Özgül Özdemir R , Özdemir A , Kırmaz C , Tuğlu M , Şenol Ö , Özverel C , Berdeli A . The effects of mesenchymal stem cells on the IDO, HLA-G and PD-L1 expression of breast tumor cells MDA-MB-231 and MCF-7. Archives of Clinical and Experimental Medicine. 2019; 4(3): 137-132.