MEZENŞİMAL KÖK HÜCRE SİTOKİNLERİNİN KANSER HÜCRELERİ ÜZERİNE OLUMSUZ ETKİLERİ / THE ADVERSE EFFECTS OF MESENCHYMAL STEM CELL CYTOKINES ON THE CANCER CELLS

Yıl 2015, Cilt: 37 Sayı: 3, 7 - 12, 19.01.2016

Erhan Şahin , Cengiz Bayçu Ayşe Koparal , Dilek Dönmez , Nuriye Bektur

Öz

Özet: Kök hücreler kararlı yapısıyla çok hücreli canlılarda bulunan bir hücre türüdür. Mezenşimal kök hücreler yetişkin tipte kök hücrelerdir. Günümüzde kök hücre tedavileri, tıbbın birçok alanında deneysel veya bazı alanlarında da klinik olarak kullanılan önemli tedavi yöntemlerindendir. Kanser, insidansı son yıllarda artan bir hastalıktır. Farklı tedavi yöntemleri kullanılmasına rağmen henüz kanseri eradike edebilecek bir tedavi mevcut değildir. Birçok deneysel çalışmada tedavi edici ve koruyucu özelliği gösterilen MKH’nin kanser modellerinde kanserli hücreleri baskıladığı ve çoğalmalarını durdurduğu bildirilmiştir. Ancak son yıllarda kanser tedavisi için kök hücrelerin kullanıldığı çalışmalarda; kök hücrelerin kanser oluşumunu tetiklediği, kitleyi büyüttüğü, yeni damarların oluşumuna ve kanserin invazyonuna yardımcı olduğu gösterilmiştir. MKH’ler ile kanser hücreleri arasındaki iletişimin MKH’lerden salınan sitokinler yardımıyla sağlandığı bilinmektedir. MKH’nin salgıladığı bu sitokinlerin varlığı ve kanserli hücreler üzerindeki etkisi MKH’lerin tedavi güvenilirliğini azaltmaktadır.
ANAHTAR KELİMELER: Mezenşimal kök hücre, Kanser, Sitokin.

THE ADVERSE EFFECTS OF MESENCHYMAL STEM CELL CYTOKINES
ON THE CANCER CELLS

Abstract: Stem cells are the cell types that found in multicellular organisms with a stable structure. The mesenchymal stem cells (MSCs) are types of adult stem cells. Stem cell therapies are very important treatment methods that are used in many areas of experimental medicine or clinical part. Cancer is widespread disease with an increasing incidence in recent years. Despite the use of different treatment methods, there has been no definitive treatment for cancer treatment yet. MSCs therapeutic and protective features have been demonstrated in various experimental studies. In cancer models, MSCs suppressed and stopped the growth of cancer cells in recent studies. However, recently the stem cells used in cancer treatment studies trigger the formation of cancer, make larger its mass, help the formation of new vessels and lead to cancer invasion. The communication between cancer cells and MSCs are known to be done with MSCs released cytokines. The presence of these cytokines that secreted by MSCs and effects on cancer cells reduces the reliability of MSC treatment.
KEYWORDS: Mesenchymal stem cells, Cancer, Cytokine

Anahtar Kelimeler

-

Kaynakça

• Razmkhah, M., Jaberipour, M., Erfani, N., Habibagahi, M., Talei, A.-r., and Ghaderi, A. (2011). Adipose derived stem cells (ASCs) isolated from breast cancer tissue express IL-4, IL-10 and TGF-β1 and upregulate expression of regulatory molecules on T cells: do they protect breast cancer cells from the immune response? Cellular immunology, 266(2), 116- 122.
• Yao, W., Hu, Q., Ma, Y., Xiong, W., Wu, T., Cao, J., and Wu, D. (2015). Human adipose-derived mesenchymal stem cells repair cisplatin- induced antiapoptotic pathways. Experimental and Therapeutic Medicine. injury through
• Bang, O. Y. (2015). Autologous Mesenchymal Stem Cell Therapy in Patients with Stroke Cell Therapy for Brain Injury (pp. 21-35): Springer.
• Wang, S., Qu, X., and Zhao, R. C. (2012). Clinical applications of mesenchymal stem cells. J Hematol Oncol, 5(1), 19.
• Aktaş, S. H. (2010). Kemoterapinin Kolon Kanseri, Meme Kanseri Ve Mide Kanserinde Vegf Düzeylerine Etkisinin İn Vivo Ve İn Vitro İncelemesi. (Yüksek Lisans Tezi), Ankara Üniversitesi, Ankara.
• Houghton, J., Morozov, A., Smirnova, I., and Wang, T. C. (2007). Stem cells and cancer. Seminars in Cancer Biology, 17(3), 191-203.
• Ferlay, J., Soerjomataram, I., Dikshit, R., Eser, S., Mathers, C., Rebelo, M., Bray, F. (2015). Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. International Journal of Cancer, 136(5), E359-E386.
• Heldring, N., Mäger, I., Wood, M. J., Le Blanc, K., and Andaloussi, S. E. (2015). Therapeutic Potential of Multipotent Mesenchymal Stromal Cells and Their Extracellular Vesicles. Human gene therapy, 26(8), 506-517.
• Torsvik, A., and Bjerkvig, R. (2013). Mesenchymal stem cell signaling in cancer progression. Cancer treatment reviews, 39(2), 180-188.
• Bobis, S., Jarocha, D., and Majka, M. (2007). Mesenchymal stem cells: characteristics and clinical applications. Folia Histochemica et Cytobiologica, 44(4), 215-214.
• Shah, K. (2012). Mesenchymal stem cells engineered for cancer therapy. Adv Drug Deliv Rev, 64(8), 739-748.
• Iwamoto, S., Mihara, K., Downing, J. R., Pui, C.-H., and Campana, D. (2007). Mesenchymal cells lymphoblastic leukemia cells to asparaginase. Journal of Clinical Investigation, 117(4), 1049.
• Djouad, F., Plence, P., Bony, C., Tropel, P., Apparailly, F., Sany, J., Jorgensen, C. (2003). Immunosuppressive effect of mesenchymal stem cells favors tumor growth in allogeneic animals. Blood, 102(10), 3837-3844.
• Djouad, F., Bony, C., Apparailly, F., Louis- Plence, P., Jorgensen, C., and Noël, D. (2006). Earlier onset of syngeneic tumors in the presence Transplantation, 82(8), 1060-1066. stem cells.
• Li, W., Zhou, Y., Yang, J., Zhang, X., Zhang, H., Zhang, T., Wu, H. (2015). Gastric cancer- derived mesenchymal stem cells prompt gastric cancer progression through secretion of interleukin-8. Journal of Experimental and Clinical Cancer Research, 34(1), 1-15.
• Cuiffo, Benjamin G., Campagne, A., Bell, George W., Lembo, A., Orso, F., Lien, Evan C., Karnoub, Antoine E. (2014). MSC- Regulated MicroRNAs Converge on the Transcription Factor FOXP2 and Promote Breast Cancer Metastasis. Cell Stem Cell, 15(6), 762-774.
• Liu, S., Ginestier, C., Ou, S. J., Clouthier, S. G., Patel, S. H., Monville, F., Kleer, C. G. (2011). Breast cancer stem cells are regulated by mesenchymal stem cells through cytokine networks. Cancer research, 71(2), 614-624.
• Barnes, P. J., Drazen, J. M., Rennard, S. I., and Thomson, N. C. (2009). Asthma and COPD: Academic Press.
• Jotzu, C., Alt, E., Welte, G., Li, J., Hennessy, B. T., Devarajan, E., Song, Y.-H. (2010). Adipose tissue-derived stem cells differentiate into carcinoma-associated under the influence of tumor-derived factors. Analytical cellular pathology, 33(2), 61-79.
• Mishra, P. J., Mishra, P. J., Humeniuk, R., Medina, D. J., Alexe, G., Mesirov, J. P., Banerjee, D. (2008). Carcinoma-associated fibroblast–like mesenchymal stem cells. Cancer research, 68(11), 4331-4339. of human
• Mueller, M. M., and Fusenig, N. E. (2004). Friends or foes—bipolar effects of the tumour stroma in cancer. Nature Reviews Cancer, 4(11), 839-849.
• Quante, M., Tu, S. P., Tomita, H., Gonda, T., Wang, S. S., Takashi, S., Betz, K. S. (2011). Bone marrow-derived
• myofibroblasts contribute to the mesenchymal stem cell niche and promote tumor growth. Cancer cell, 19(2), 257-272.
• Hossain, A., Gumin, J., Gao, F., Figueroa, J., Shinojima, N., Takezaki, T., Joyce, C. (2015). Mesenchymal Stem Cells Isolated from Human Gliomas Increase Proliferation and Maintain Stemness of Glioma Stem Cells Through the IL‐6/gp130/STAT3 Pathway. Stem Cells.
• Hsu, H.-S., Lin, J.-H., Hsu, T.-W., Su, K., Wang, C.-W., Yang, K.-Y., Hung, S.-C. (2012). Mesenchymal stem cells enhance lung cancer initiation through activation of IL- 6/JAK2/STAT3 pathway. Lung Cancer, 75(2), 167-177.
• Tsai, K. S., Yang, S. H., Lei, Y. P., Tsai, C. C., Chen, H. W., Hsu, C. Y., Chiou, S. H. (2011). Mesenchymal stem cells promote formation of colorectal tumors in mice. Gastroenterology, 141(3), 1046-1056.
• Barbero, S., Bonavia, R., Bajetto, A., Porcile, C., Pirani, P., Ravetti, J. L., Schettini, G. (2003). Stromal cell-derived factor 1α stimulates human glioblastoma cell growth through the activation of both extracellular signal-regulated kinases 1/2 and Akt. Cancer research, 63(8), 1969-1974.
• Ignatov, A., Robert, J., Gregory‐Evans, C., and Schaller, H. (2006). RANTES stimulates Ca2+ mobilization and inositol trisphosphate (IP3) formation in cells transfected with G protein‐ coupled receptor 75. British journal of pharmacology, 149(5), 490-497.
• Chen, D., Liu, S., Ma, H., Liang, X., Ma, H., Yan, X., Liu, X. (2015). Paracrine factors from adipose-mesenchymal stem cells enhance metastatic capacity through Wnt signaling pathway in a colon cancer cell co-culture model. Cancer Cell International, 15(1), 42.
• Zhang, L., Sun, J., Liu, Z., Dai, Y., Luo, Z., Jiang, X., Li, G. (2014). Mesenchymal stem cells regulate cytoskeletal dynamics and promote cancer cell invasion through low dose nitric oxide. Curr Mol Med, 14(6), 749-761.
• Lee, M. J., Heo, S. C., Shin, S. H., Kwon, Y. W., Do, E. K., Suh, D. S., Kim, J. H. (2013). Oncostatin M promotes mesenchymal stem cell-stimulated tumor growth through a paracrine mechanism involving periostin and TGFBI. Int J Biochem Cell Biol, 45(8), 1869- 1877.
• De Luca, A., Lamura, L., Gallo, M., Maffia, V., and Normanno, N. (2012). Mesenchymal stem cell-derived endothelial growth factor promote breast cancer cell migration. J Cell Biochem, 113(11), 3363-3370. and vascular