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

Saglam O., Unal Z. S., Subasi C., Ulukaya E., Karaoz E.

TUMOR BIOLOGY, cilt.36, sa.7, ss.5667-5677, 2015 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 36 Sayı: 7
  • Basım Tarihi: 2015
  • Doi Numarası: 10.1007/s13277-015-3241-5
  • Dergi Adı: TUMOR BIOLOGY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.5667-5677
  • Anahtar Kelimeler: IL-6, Tumor microenvironment, Mesenchymal stromal cells, Breast cancer, STEM-CELLS, TUMOR-MICROENVIRONMENT, MOLECULAR CHARACTERIZATION, IN-VIVO, GROWTH, PROGRESSION, METASTASIS, COCULTURE
  • Kocaeli Üniversitesi Adresli: Evet

Özet

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.