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Stem cells affect cytokine responses in the microenvironment of tumor cells: Interaction between breast cancer and dental pulp stem cells

Year 2021, Volume: 60 Issue: 4, 314 - 323, 22.12.2021

Sayra Dilmaç , Mustafa Gökhan Ertosun Eda Açıkgöz , Gamze Tanrıöver

https://doi.org/10.19161/etd.1036959

Abstract

Aim: Tumor and surrounding microenvironment cells are closely related and interact constantly. The mutual communication between these cells may affect some factors such as cytokines that involved in tumor progression and metastasis. In the interactions between stem cells and their niches; It is known to be reciprocal similar to tumor cells. Transforming Growth Factor Beta1 and Growth Differentiation Factor15 are cytokines which have dual effects on the tumor microenvironment. In our study, we aimed to investigate the effects of interaction of tumor cells and stem cells on cytokine responses in their microenvironment.
Materials and Methods: Dental pulp stem cells and MDA-MB-231 cells were used in co-culture experiments in this study. MDA-MB-231 and Dental Pulp Stem Cells were cultured both individually and together in different combinations and their conditional media were collected. Transforming Growth Factor Beta1 and Growth Differentiation Factor15 cytokine levels in conditional media were determined by using ELISA.
Results: Expression of Transforming Growth Factor Beta1 and Growth Differentiation Factor15 increased in Dental Pulp Stem Cell medium incubated with conditional media from MDA-MB-231 cells, but there was no difference in these cytokine levels in media taken from individual cell lines. Increasing these selected cytokine responses will affect the metastasis potential of tumor cells.
Conclusion: We observed that cross-talks between tumor cells and stem cells alters the responses of cytokines in the tumor microenvironment and affects tumor progression. Therefore, our study emphasizes the importance of the tumor microenvironment in tumor responses, and may contribute to the new perspectives in this respect.

Keywords

Triple Negative Breast Cancer Dental Pulp Stem Cells conditional media Transforming Growth Factor Beta1 Growth Differentiation Factor15

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Kök hücreler kanser hücrelerinin mikroçevresindeki sitokin yanıtlarını etkiler: Meme kanseri ve dental pulpa kök hücreleri arasındaki etkileşim

Year 2021, Volume: 60 Issue: 4, 314 - 323, 22.12.2021

Sayra Dilmaç , Mustafa Gökhan Ertosun Eda Açıkgöz , Gamze Tanrıöver

https://doi.org/10.19161/etd.1036959

Abstract

Amaç: Tümör ve mikroçevresinde bulunan hücreler birbirleri ile yakından ilişkilidir ve sürekli etkileşim halindedirler. Bu hücreler arasındaki karşılıklı etkileşim, tümörün gelişmesi ve metastazında rol oynayan sitokin yanıtlarını şekillendirir. Kök hücreler ile bunların nişleri arasındaki etkileşimlerin de; tümör hücrelerine benzer şekilde karşılıklı olduğu bilinmektedir. Dönüştürücü Büyüme Faktörü Beta1 ve Büyüme/farklılaşma faktörü15, tümör mikroçevresi üzerinde çift yönlü etkileri olan sitokinlerdir. Çalışmamızda, tümör hücreleri ve kök hücrelerin karşılıklı etkileşimlerinin mikroçevrelerindeki sitokin yanıtlarına olan etkilerini araştırmayı amaçladık.
Gereç ve Yöntem: Bu çalışmada ko-kültür deneyleri için Dental pulpa kök hücreleri ile MDA-MB-231 meme kanseri hücreleri kullanılmıştır. MDA-MB-231 ve Dental Pulpa Kök Hücreleri hem bireysel hem de birlikte farklı kombinasyonlarla kültüre edildi ve koşullu medyumları toplandı. Toplanan koşullu medyumlarda Dönüştürücü Büyüme Faktörü Beta1 ve Büyüme/farklılaşma faktörü15 sitokin seviyeleri ELISA yöntemi ile değerlendirildi.
Bulgular: MDA-MB-231 hücrelerinin koşullu medyumları ile inkübe edilen Dental pulpa kök hücre medyumunda Dönüştürücü Büyüme Faktörü Beta1 ve Büyüme/farklılaşma faktörü15 ekspresyonlarının arttığı ancak, tek tek hücre hatlarından alınan medyumlarda bu sitokin seviyelerinde fark olmadığı görüldü. Seçilen bu sitokin yanıtlarının artması tümör hücrelerinin metastaz potansiyellerini etkileyeceğinden önem içermektedir.
Sonuç: Tümör hücreleri ve kök hücreler arasındaki karşılıklı konuşma, tümör mikroçevresindeki sitokinlerin yanıtlarını değiştirir ve tümörün metastaz potansiyelini etkileyebilir. Dolayısıyla çalışmamız tümör mikroçevresinin, tümörün gelecek yanıtlarında önemini vurgulayan bir çalışma olma nitelinde olup bu yönüyle literatüre katkı sağlayacaktır.

Keywords

Üçlü Negatif Meme Kanseri Dental Pulpa Kök Hücreleri koşullu medyum Dönüştürücü Büyüme Faktörü Beta1 Büyüme/farklılaşma faktörü15

References

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  • Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136 (5): E359-86.
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  • Nedeljkovic M, Damjanovic A. Mechanisms of Chemotherapy Resistance in Triple-Negative Breast Cancer-How We Can Rise to the Challenge. Cells. 2019; 8 (9).
  • Chen F, Zhuang X, Lin L, Yu P, Wang Y, Shi Y, et al. New horizons in tumor microenvironment biology: challenges and opportunities. BMC Med. 2015;13:45.
  • Wang M, Zhao J, Zhang L, Wei F, Lian Y, Wu Y, et al. Role of tumor microenvironment in tumorigenesis. J Cancer. 2017; 8 (5): 761-73.
  • Hanahan D, Coussens LM. Accessories to the crime: functions of cells recruited to the tumor microenvironment. Cancer Cell. 2012; 21 (3): 309-22.
  • Dvorak HF. Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med. 1986; 315 (26): 1650-9.
  • Waldmann TA. Cytokines in Cancer Immunotherapy. Cold Spring Harb Perspect Biol. 2018;10 (12).
  • Alexander WS, Hilton DJ. The role of suppressors of cytokine signaling (SOCS) proteins in regulation of the immune response. Annu Rev Immunol. 2004;22:503-29.
  • Massague J. How cells read TGF-beta signals. Nat Rev Mol Cell Biol. 2000;1(3):169-78.
  • Gordon KJ, Blobe GC. Role of transforming growth factor-beta superfamily signaling pathways in human disease. Biochim Biophys Acta. 2008; 1782 (4): 197-228.
  • Dunning AM, Ellis PD, McBride S, Kirschenlohr HL, Healey CS, Kemp PR, et al. A transforming growth factorbeta1 signal peptide variant increases secretion in vitro and is associated with increased incidence of invasive breast cancer. Cancer Res. 2003; 63 (10): 2610-5.
  • Bootcov MR, Bauskin AR, Valenzuela SM, Moore AG, Bansal M, He XY, et al. MIC-1, a novel macrophage inhibitory cytokine, is a divergent member of the TGF-beta superfamily. Proc Natl Acad Sci U S A. 1997;94 (21): 11514-9.
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  • Li S, Ma YM, Zheng PS, Zhang P. GDF15 promotes the proliferation of cervical cancer cells by phosphorylating AKT1 and Erk1/2 through the receptor ErbB2. J Exp Clin Cancer Res. 2018; 37 (1): 80.
  • Corre J, Labat E, Espagnolle N, Hebraud B, Avet-Loiseau H, Roussel M, et al. Bioactivity and prognostic significance of growth differentiation factor GDF15 secreted by bone marrow mesenchymal stem cells in multiple myeloma. Cancer Res. 2012; 72 (6): 1395-406.
  • Mehta RS, Chong DQ, Song M, Meyerhardt JA, Ng K, Nishihara R, et al. Association Between Plasma Levels of Macrophage Inhibitory Cytokine-1 Before Diagnosis of Colorectal Cancer and Mortality. Gastroenterology. 2015; 149 (3): 614-22.
  • Wang T, Mao B, Cheng C, Zou Z, Gao J, Yang Y, et al. YAP promotes breast cancer metastasis by repressing growth differentiation factor-15. Biochim Biophys Acta Mol Basis Dis. 2018;1864(5 Pt A):1744-53.
  • Tran C, Damaser MS. Stem cells as drug delivery methods: application of stem cell secretome for regeneration. Adv Drug Deliv Rev. 2015; 82-83: 1-11.
  • Zhang CL, Huang T, Wu BL, He WX, Liu D. Stem cells in cancer therapy: opportunities and challenges. Oncotarget. 2017; 8 (43): 75756-66.
  • Razmkhah M, Jaberipour M, Hosseini A, Safaei A, Khalatbari B, Ghaderi A. Expression profile of IL-8 and growth factors in breast cancer cells and adipose-derived stem cells (ASCs) isolated from breast carcinoma. Cell Immunol. 2010; 265 (1): 80-5.
  • Ning H, Lin G, Fandel T, Banie L, Lue TF, Lin CS. Insulin growth factor signaling mediates neuron-like differentiation of adipose-tissue-derived stem cells. Differentiation. 2008; 76 (5): 488-94.
  • Song YH, Gehmert S, Sadat S, Pinkernell K, Bai X, Matthias N, et al. VEGF is critical for spontaneous differentiation of stem cells into cardiomyocytes. Biochem Biophys Res Commun. 2007; 354 (4): 999-1003.
  • Kim WS, Park SH, Ahn SJ, Kim HK, Park JS, Lee GY, et al. Whitening effect of adipose-derived stem cells: a critical role of TGF-beta 1. Biol Pharm Bull. 2008; 31 (4): 606-10.
  • Dirat B, Bochet L, Dabek M, Daviaud D, Dauvillier S, Majed B, et al. Cancer-associated adipocytes exhibit an activated phenotype and contribute to breast cancer invasion. Cancer Res. 2011; 71 (7): 2455-65.
  • Rowan BG, Gimble JM, Sheng M, Anbalagan M, Jones RK, Frazier TP, et al. Human adipose tissue-derived stromal/stem cells promote migration and early metastasis of triple negative breast cancer xenografts. PLoS One. 2014; 9 (2): e89595.
  • Testa U, Castelli G, Pelosi E. Breast Cancer: A Molecularly Heterogenous Disease Needing Subtype-Specific Treatments. Med Sci (Basel). 2020; 8 (1).
  • Vagia E, Mahalingam D, Cristofanilli M. The Landscape of Targeted Therapies in TNBC. Cancers (Basel). 2020; 12 (4).
  • Hu M, Yao J, Cai L, Bachman KE, van den Brule F, Velculescu V, et al. Distinct epigenetic changes in the stromal cells of breast cancers. Nat Genet. 2005; 37 (8): 899-905.
  • Soysal SD, Tzankov A, Muenst SE. Role of the Tumor Microenvironment in Breast Cancer. Pathobiology. 2015; 82 (3-4): 142-52.
  • Coleman RE, Gregory W, Marshall H, Wilson C, Holen I. The metastatic microenvironment of breast cancer: clinical implications. Breast. 2013; 22 Suppl 2:S50-6.
  • Folgueira MA, Maistro S, Katayama ML, Roela RA, Mundim FG, Nanogaki S, et al. Markers of breast cancer stromal fibroblasts in the primary tumour site associated with lymph node metastasis: a systematic review including our case series. Biosci Rep. 2013; 33(6).
  • Luster AD, Alon R, von Andrian UH. Immune cell migration in inflammation: present and future therapeutic targets. Nat Immunol. 2005; 6 (12):1182-90.
  • Nagarsheth N, Wicha MS, Zou W. Chemokines in the cancer microenvironment and their relevance in cancer immunotherapy. Nat Rev Immunol. 2017;17 (9): 559-72.
  • Taniguchi K, Karin M. NF-kappaB, inflammation, immunity and cancer: coming of age. Nat Rev Immunol. 2018; 18 (5): 309-24.
  • Wang J, Li D, Cang H, Guo B. Crosstalk between cancer and immune cells: Role of tumor-associated macrophages in the tumor microenvironment. Cancer Med. 2019; 8 (10): 4709-21.
  • Young MR, Wright MA. Myelopoiesis-associated immune suppressor cells in mice bearing metastatic Lewis lung carcinoma tumors: gamma interferon plus tumor necrosis factor alpha synergistically reduces immune suppressor and tumor growth-promoting activities of bone marrow cells and diminishes tumor recurrence and metastasis. Cancer Res. 1992; 52 (22): 6335-40.
  • Ridge SM, Sullivan FJ, Glynn SA. Mesenchymal stem cells: key players in cancer progression. Mol Cancer. 2017;16 (1): 31.
  • Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, et al. Multilineage potential of adult human mesenchymal stem cells. Science. 1999; 284 (5411): 143-7.
  • Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006; 8 (4): 315-7.
  • Gronthos S, Mankani M, Brahim J, Robey PG, Shi S. Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proc Natl Acad Sci U S A. 2000; 97 (25): 13625-30.
  • Friedenstein AJ, Chailakhjan RK, Lalykina KS. The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells. Cell Tissue Kinet. 1970; 3 (4): 393-403.
  • Chamberlain G, Fox J, Ashton B, Middleton J. Concise review: mesenchymal stem cells: their phenotype, differentiation capacity, immunological features, and potential for homing. Stem Cells. 2007; 25 (11): 2739-49.
  • Sprio AE, Di Scipio F, Raimondo S, Salamone P, Pagliari F, Pagliari S, et al. Self-renewal and multipotency coexist in a long-term cultured adult rat dental pulp stem cell line: an exception to the rule? Stem Cells Dev. 2012;21(18):3278-88.
  • Hilkens P, Fanton Y, Martens W, Gervois P, Struys T, Politis C, et al. Pro-angiogenic impact of dental stem cells in vitro and in vivo. Stem Cell Res. 2014; 12 (3): 778-90.
  • Yalvac ME, Yarat A, Mercan D, Rizvanov AA, Palotas A, Sahin F. Characterization of the secretome of human tooth germ stem cells (hTGSCs) reveals neuro-protection by fine-tuning micro-environment. Brain Behav Immun. 2013; 32: 122-30.
  • Bachman KE, Park BH. Duel nature of TGF-beta signaling: tumor suppressor vs. tumor promoter. Curr Opin Oncol. 2005; 17 (1): 49-54.
  • Janda E, Lehmann K, Killisch I, Jechlinger M, Herzig M, Downward J, et al. Ras and TGF[beta] cooperatively regulate epithelial cell plasticity and metastasis: dissection of Ras signaling pathways. J Cell Biol. 2002; 156 (2): 299-313.
  • Zarzynska JM. Two faces of TGF-beta1 in breast cancer. Mediators Inflamm. 2014;2014:141747.
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There are 65 citations in total.

Details

Primary Language Turkish
Subjects Health Care Administration
Journal Section Research Articles
Authors

Sayra Dilmaç 0000-0002-1080-6791

Mustafa Gökhan Ertosun 0000-0002-2557-7346

Eda Açıkgöz 0000-0002-6772-3081

Gamze Tanrıöver 0000-0002-8002-5544

Publication Date December 22, 2021
Submission Date February 13, 2021
Published in Issue Year 2021Volume: 60 Issue: 4

Cite

Vancouver Dilmaç S, Ertosun MG, Açıkgöz E, Tanrıöver G. Kök hücreler kanser hücrelerinin mikroçevresindeki sitokin yanıtlarını etkiler: Meme kanseri ve dental pulpa kök hücreleri arasındaki etkileşim. EJM. 2021;60(4):314-23.
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