Cancer-Associated Fibroblasts Regulate the Plasticity of Breast Cancer Stemness through the Production of Leukemia Inhibitory Factor

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Küçük Resim

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