A positive feedback loop driven by fibronectin and IL-1β sustains the inflammatory microenvironment in breast cancer

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TUNALI G., Yanik H., ÖZTÜRK S. C., DEMİRKOL CANLI S., Efthymiou G., Yilmaz K. B., ...Daha Fazla

Breast cancer research : BCR, cilt.25, sa.1, ss.27, 2023 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 25 Sayı: 1
  • Basım Tarihi: 2023
  • Doi Numarası: 10.1186/s13058-023-01629-0
  • Dergi Adı: Breast cancer research : BCR
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, CAB Abstracts, CINAHL, EMBASE, MEDLINE, Veterinary Science Database, Directory of Open Access Journals
  • Sayfa Sayıları: ss.27
  • Anahtar Kelimeler: Fibronectin, Triple-negative breast cancer, Inflammation, Tumor-associated macrophage, STAT3, NF-kappa B
  • Hacettepe Üniversitesi Adresli: Evet

Özet

Inflammatory alterations of the extracellular matrix shape the tumor microenvironment and promote all stages of carcinogenesis. This study aims to determine the impact of cellular fibronectin on inflammatory facets of tumor-associated macrophages (TAMs) in breast cancer. Cellular fibronectin (FN) harboring the alternatively spliced extra domain A (FN-EDA) was determined to be a matrix component produced by the triple-negative breast cancer (TNBC) cells. High levels of FN-EDA correlated with poor survival in breast cancer patients. The proinflammatory cytokine IL-1β enhanced the expression of cellular fibronectin including FN-EDA. TAMs were frequently observed in the tumor areas rich in FN-EDA. Conditioned media from TNBC cells induced the differentiation of CD206+CD163+ macrophages and stimulated the STAT3 pathway, ex vivo. In the macrophages, the STAT3 pathway enhanced FN-EDA-induced IL-1β secretion and NF-κB signaling. In conclusion, our data indicate a self-reinforcing mechanism sustained by FN-EDA and IL-1β through NF-κB and STAT3 signaling in TAMs which fosters an inflammatory environment in TNBC.