Cancer-Associated Fibroblasts Regulate the Plasticity of Breast Cancer Stemness through the Production of Leukemia Inhibitory Factor
Yükleniyor...
Dosyalar
Tarih
2021
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Multidisciplinary Digital Publishing Institute (MDPI)
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Leukemia inhibitory factor (LIF), as a member of the interleukin-6 cytokine family, plays a complex role in solid tumors. However, the effect of LIF as a tumor microenvironment factor on plasticity control in breast cancer remains largely unknown. In this study, an in vitro investigation is conducted to determine the crosstalk between breast cancer cells and fibroblasts. Based on the results, cancer-associated fibroblasts are producers of LIF in the cocultivation system with breast cancer cells. Treatment with the CAF-CM and human LIF protein significantly promoted stemness through the dedifferentiation process and regaining of stem-cell-like properties. In addition, the results indicate that activation of LIFR signaling in breast cancer cells in the existence of CAF-secreted LIF can induce Nanog and Oct4 expression and increase breast cancer stem cell markers CD24?/CD44+. In contrast, suppression of the LIF receptor by human LIF receptor inhibition antibody decreased the cancer stem cell markers. We found that LIF was frequently overexpressed by CAFs and that LIF expression is necessary for dedifferentiation of breast cancer cell phenotype and regaining of cancer stem cell properties. Our results suggest that targeting LIF/LIFR signaling might be a potent therapeutic strategy for breast cancer and the prevention of tumor recurrence.
Açıklama
Anahtar Kelimeler
Breast Cancer, Cancer Stem Cell, Cancer-associated Fibroblasts, Leukemia Inhibitory Factor, LIF/LIFR Signaling Pathway
Kaynak
Life
WoS Q Değeri
Q2
Scopus Q Değeri
Q2
Cilt
11
Sayı
12
Künye
Vaziri, N., Shariati, L., Zarrabi, A., Farazmand, A., & Javanmard, S. H. (2021). Cancer-associated fibroblasts regulate the plasticity of breast cancer stemness through the production of leukemia inhibitory factor. Life, 11(12) doi:10.3390/life11121298
