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IL-6 originated from breast cancer tissue-derived mesenchymal stromal cells may contribute to carcinogenesis

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Tumor Biology

Abstract

Tumor microenvironment is an important factor, which sustains and promotes the tumors by inflammatory signals. Interleukin-6 (IL-6) is known as a multifunctional cytokine, which is a major activator of the signaling pathway of Janus kinases (JAKs)/signal transducer and activator of transcription 3 (STAT3). In this study, we aimed to investigate the effect of IL-6 in the tumor microenvironment on carcinogenesis. For this purpose, healthy breast tissue-derived stromal cells (HBT-SCs) and malign breast tissue-derived stromal cells (MBT-SCs) were co-cultured with MCF-7 (human breast adenocarcinoma cell line) cells using semipermeable membranes. The cell proliferation was monitored with water-soluble tetrazolium (WST) and carboxyfluorescein succinimidyl ester (CFSE) assays. Protein levels were measured by enzyme-linked immunosorbent assay (ELISA) and Western blot hybridization, while gene expressions were measured by real-time PCR. The results demonstrated that IL-6 protein levels increased significantly in the supernatants of MBT-SCs when they were co-cultured with MCF-7 cells. In accordance with this, the expression of IL-6 was significantly higher in MBT-SCs. Additionally, the expression of STAT3 in MCF-7 cells increased slightly when they were co-cultured with MBT-SCs. Considering together, there is an important interaction between tumor microenvironment and tumor cells mediated by IL-6 signaling. Thereby, the targeting on IL-6 signaling in the treatment of cancer might effectively prevent the tumor progression.

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Acknowledgments

We thank Dr. Gulçin Gacar and Gülay Erman for their technical assistance. The authors are also grateful to Dr. Murat Kasap and Dr. Gökhan Duruksu for their helpful comments on this study. We are grateful to Neslihan Onder who is a lecturer for English literature at the University of Uludağ.

Ethical standards

All of the biological materials used in this study were collected after the approval of the Ethics Committee (2009/112 I.E. 13/18) of Kocaeli University

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None

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Authors and Affiliations

  1. Center for Stem Cell and Gene Therapies Research and Practice, Department of Stem Cell, Kocaeli University, Kocaeli, Turkey

    Özlem Sağlam, Zehra Seda Ünal & Cansu Subaşı

  2. Department of Medical Biochemistry, Uludağ University, Bursa, Turkey

    Engin Ulukaya

  3. Liv Hospital, Center for Regenerative Medicine and Stem Cell Research & Manufacturing (LivMedCell), İstanbul, Turkey

    Erdal Karaöz

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  1. Özlem Sağlam
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  2. Zehra Seda Ünal
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  3. Cansu Subaşı
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  4. Engin Ulukaya
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  5. Erdal Karaöz
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Correspondence to Erdal Karaöz.

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Sağlam, Ö., Ünal, Z.S., Subaşı, C. et al. IL-6 originated from breast cancer tissue-derived mesenchymal stromal cells may contribute to carcinogenesis. Tumor Biol. 36, 5667–5677 (2015). https://doi.org/10.1007/s13277-015-3241-5

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  • DOI: https://doi.org/10.1007/s13277-015-3241-5

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