骨髓瘤细胞衍生CCL2通过瘤相关巨细胞的积累促进肺转移
Hiroya Kondo1, Hiroshi Tazawa2,3, Tomohiro Fujiwara1,4
1Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, 700-8558, Japan.
Cancer immunology, immunotherapy : CII
|May 9, 2025
概括
骨髓瘤肺转移是由CCL2驱动的,CCL2可以招募与瘤相关的巨细胞 (TAMs). 中和CCL2显著减少了肺组织中的转移和TAMs.
科学领域:
- 在瘤学瘤学.
- 癌症生物学 癌症生物学
- 免疫学 免疫学 免疫学
背景情况:
- 骨髓瘤 (OS) 是儿童和青少年常见的一种骨癌.
- 肺转移显著恶化OS患者的预后.
- 驱动OS肺转移的机制,特别是瘤微环境 (TME),尚未完全理解.
研究的目的:
- 调查TME在骨髓瘤肺转移中的作用.
- 确定促进OS转移的关键因素.
- 评估CCL2作为减少OS肺转移的治疗标.
主要方法:
- 使用了与非转移和转移小鼠 (Dunn, LM8) 和人类 (HOS, 143B) OS细胞的 ортотоп模型.
- 使用细胞因子阵列和ELISA分析了TME并确定了OS细胞分泌的因子.
- 在体内给予CCL2中和抗体以评估治疗潜力.
主要成果:
- 转移性OS细胞显示M2类瘤相关巨细胞 (TAMs) 在肺组织的透增加.
- 转移性OS细胞通常通过细胞外囊泡分泌CCL2,部分通过细胞外囊泡.
- 中和CCL2抗体抑制了肺转移和M2样TAM透,但没有影响原发性瘤生长.
结论:
- CCL2是促进骨髓瘤肺转移的关键因素.
- CCL2通过增加肺部M2样TAM积累来促进转移.
- 向CCL2显示了抑制骨髓瘤肺转移的治疗潜力.
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