title: IL-6 originated from breast cancer tissue-derived mesenchymal stromal cells may contribute to carcinogenesis.
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.
authors.affiliation: Center for Stem Cell and Gene Therapies Research and Practice, Department of Stem Cell, Kocaeli University, Kocaeli, Turkey.
authors.forename: Özlem
authors.initials: Ö
authors.lastname: Sağlam
authors.forename: Zehra Seda
authors.initials: ZS
authors.lastname: Ünal
authors.forename: Cansu
authors.initials: C
authors.lastname: Subaşı
authors.forename: Engin
authors.initials: E
authors.lastname: Ulukaya
authors.forename: Erdal
authors.initials: E
authors.lastname: Karaöz
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000235:genetics; D018920:Coculture Techniques; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D061986:MCF-7 Cells; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000473:pathology; D050796:STAT3 Transcription Factor / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction; D059016:Tumor Microenvironment / Q000235:genetics*
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human