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Abstract

Breast cancer is a complex heterogeneous disease that poses significant challenges in identifying novel therapeutic strategies and new therapeutic targets. Recent research has identified adipose-derived stem cells (ASCs) role in the progression of small tumors. Mutations in Breast Cancer gene 1 (BRCA1) are known to play a crucial role in DNA repair and cell cycle regulation. BRCA1 mutations have been associated with increased risks of breast and ovarian cancer. Moreover, studies have shown that Fibroblast Growth Factor Receptor 1 (FGFR1) is involved in initiation of many cancers, including breast cancer. In the present study, we aim to investigate the role of FGFR1 in BRCA1-negative ASCs and its therapeutic potential in breast cancer. Using AZD4547 to knockdown FGFR1 expression in BRCA1 mutant ASCs in vitro and in vivo. Our results showed that FGFR1 knockdown significantly inhibited the release of pro-inflammatory cytokines, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α ) from BRCA1 mutant ASCs. Furthermore, FGFR1 knockdown has significantly decreased proliferation, migration, and invasion of breast cancer cells co-cultured with BRCA1 mutant ASCs. Xenograft studies have confirmed reduced tumor growth and metastasis via Vascular Endothelial Growth Factor A (VEGFA) expression inhibition and Nuclear factor kappa-B cells (NF-κ B) pathway downregulation. Collectively, our results emphasize the critical role of FGFR1 in BRCA1 mutant ASCs in the progression of breast cancer through inflammatory cytokines regulation. Moreover, our results suggest that targeting FGFR1 in tumor microenvironment, specifically in BRCA1 mutant ASCs, may be a promising therapeutic approach in breast cancer treatment. However, further clinical studies are needed.

Keywords

Adipose-derived stem cells (ASCs), BRCA1 mutations, Fibroblast growth factor receptor 1 (FGFR1), Interleukin-6 (IL-6), Pro-inflammatory cytokines, Tumor necrosis factor-alpha (TNF-α )

Subject Area

Chemistry

Article Type

Article

First Page

807

Last Page

817

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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