Abstract 5523: granulocyte-colony stimulating factor secreted from cancer associated fibroblasts initiates tumorigenesis and metastasis in triple negative breast cancer

Abstract

Abstract Although cancer stem-like cells (CSCs) interact with cancer-associated fibroblasts (CAFs), it remains obscure how it occurs and what are the functional roles of this interaction. When patient-derived breast cancer cells (BCCs) were co-cultured with CAFs, significantly more spheroids were formed compared to those cells cultured alone. This suggests that CAFs produce soluble factors that increase the tumor-initiating ability of CSCs. Transcriptome analysis revealed that the expression of granulocyte colony stimulating factor (G-CSF) was highly upregulated in the conditioned medium of CAFs co-cultured with BCCs. Tumor-initiating ability was increased in the presence of G-CSF. Furthermore, G-CSF neutralizing antibody treatment suppressed tumorigenesis and bone metastasis in the patient-derived xenograft (PDX) model. These findings indicate that G-CSF secreted by CAFs induces CSCs to initiate tumors and metastasis. Inhibition of G-CSF would be a novel therapeutic target for breast cancer. Citation Format: Noriko Gotoh, Yasuto Tacheuchi, Takahiko Murayama, Risa Kashimura, Kazuhiro Ikeda, Kuniko Horie, Satoshi Inoue, Koji Okamoto. granulocyte-colony stimulating factor secreted from cancer associated fibroblasts initiates tumorigenesis and metastasis in triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5523.