神经生长因子促进骨肉瘤微环境中依赖 VCAM-1 的单核细胞粘附和 M2 极化:拉罗替尼疗法的意义。

IF 8.2 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
International Journal of Biological Sciences Pub Date : 2024-08-01 eCollection Date: 2024-01-01 DOI:10.7150/ijbs.95463
Syuan-Ling Lin, Shang-Yu Yang, Chun-Hao Tsai, Yi-Chin Fong, Wei-Li Chen, Ju-Fang Liu, Chih-Yang Lin, Chih-Hsin Tang
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引用次数: 0

摘要

骨肉瘤是最常见的原发性恶性骨肿瘤,主要影响儿童和青少年。被称为神经营养素的神经生长因子(NGF)与癌症诱发的骨痛有关;然而,NGF在骨肉瘤中的作用尚未阐明。在基因组数据共享数据门户的骨肉瘤样本中,我们检测到了较高水平的NGF和M2巨噬细胞标记物,但没有检测到M1巨噬细胞标记物。细胞实验表明,NGF刺激的骨肉瘤条件培养基可促进巨噬细胞从M0表型极化为M2表型。NGF还通过FAK和c-Src级联下调miR-513c-5p水平,从而增强骨肉瘤微环境中依赖VCAM-1的单核细胞粘附性。在体内异种移植模型中,NGF 的过表达被证明能促进肿瘤生长,而口服 TrK 抑制剂 larotrectinib 能明显拮抗 NGF 促进的 M2 巨噬细胞表达和肿瘤进展。这些结果表明,拉罗替尼有可能作为一种治疗药物,用于缓解NGF介导的骨肉瘤进展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Nerve growth factor promote VCAM-1-dependent monocyte adhesion and M2 polarization in osteosarcoma microenvironment: Implications for larotrectinib therapy.

Osteosarcoma is the most prevalent form of primary malignant bone tumor, primarily affecting children and adolescents. The nerve growth factors (NGF) referred to as neurotrophins have been associated with cancer-induced bone pain; however, the role of NGF in osteosarcoma has yet to be elucidated. In osteosarcoma samples from the Genomic Data Commons data portal, we detected higher levels of NGF and M2 macrophage markers, but not M1 macrophage markers. In cellular experiments, NGF-stimulated osteosarcoma conditional medium was shown to facilitate macrophage polarization from the M0 to the M2 phenotype. NGF also enhanced VCAM-1-dependent monocyte adhesion within the osteosarcoma microenvironment by down-regulating miR-513c-5p levels through the FAK and c-Src cascades. In in vivo xenograft models, the overexpression of NGF was shown to enhance tumor growth, while the oral administration of the TrK inhibitor larotrectinib markedly antagonized NGF-promoted M2 macrophage expression and tumor progression. These results suggest that larotrectinib could potentially be used as a therapeutic agent aimed at mitigating NGF-mediated osteosarcoma progression.

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来源期刊
International Journal of Biological Sciences
International Journal of Biological Sciences 生物-生化与分子生物学
CiteScore
16.90
自引率
1.10%
发文量
413
审稿时长
1 months
期刊介绍: The International Journal of Biological Sciences is a peer-reviewed, open-access scientific journal published by Ivyspring International Publisher. It dedicates itself to publishing original articles, reviews, and short research communications across all domains of biological sciences.
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