Department of Respiratory Medicine and Rheumatology, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan.
Department of Pathology and Laboratory Medicine, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan.
Cancer Lett. 2018 May 1;421:17-27. doi: 10.1016/j.canlet.2018.02.016. Epub 2018 Feb 12.
Cancer stem cells (CSCs) represent a minor population that have clonal tumor initiation and self-renewal capacity and are responsible for tumor initiation, metastasis, and therapeutic resistance. CSCs reside in niches, which are composed of diverse types of stromal cells and extracellular matrix components. These stromal cells regulate CSC-like properties by providing secreted factors or by physical contact. Fibrocytes are differentiated from bone marrow-derived CD14 monocytes and have features of both macrophages and fibroblasts. Accumulating evidence has suggested that stromal fibrocytes might promote cancer progression. However, the role of fibrocytes in the CSC niches has not been revealed. We herein report that human fibrocytes enhanced the CSC-like properties of lung cancer cells through secreted factors, including osteopontin, CC-chemokine ligand 18, and plasminogen activator inhibitor-1. The PIK3K/AKT pathway was critical for fibrocytes to mediate the CSC-like functions of lung cancer cells. In human lung cancer specimens, the number of tumor-infiltrated fibrocytes was correlated with high expression of CSC-associated protein in cancer cells. These results suggest that fibrocytes may be a novel cell population that regulates the CSC-like properties of lung cancer cells in the CSC niches.
癌症干细胞（CSCs）是一小部分具有克隆肿瘤起始和自我更新能力的细胞，负责肿瘤的起始、转移和治疗抵抗。CSCs 存在于龛位中，龛位由多种类型的基质细胞和细胞外基质成分组成。这些基质细胞通过提供分泌因子或通过物理接触来调节 CSC 样特性。纤维细胞由骨髓来源的 CD14 单核细胞分化而来，具有巨噬细胞和成纤维细胞的特征。越来越多的证据表明，基质纤维细胞可能促进癌症的进展。然而，纤维细胞在 CSC 龛位中的作用尚未揭示。我们在此报告称，人纤维细胞通过分泌骨桥蛋白、CC 趋化因子配体 18 和纤溶酶原激活物抑制剂 1 等因子增强了肺癌细胞的 CSC 样特性。PI3K/AKT 通路对纤维细胞介导肺癌细胞的 CSC 样功能至关重要。在人肺癌标本中，肿瘤浸润纤维细胞的数量与癌细胞中 CSC 相关蛋白的高表达相关。这些结果表明，纤维细胞可能是一种新的细胞群体，可调节 CSC 龛位中肺癌细胞的 CSC 样特性。
