Liu Meng-Qiu, Bao Chun-Jie, Liang Xiao-Fei, Ji Xin-Yue, Zhao Li-Qiang, Yao An-Ni, Guo Sheng, Duan Jia-Lun, Zhao Ming, Duan Jin-Ao
Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Province Key Laboratory of High Technology Research, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Province Key Laboratory of High Technology Research, Nanjing University of Chinese Medicine, Nanjing 210023, China; School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Int J Biol Macromol. 2024 Mar;261(Pt 1):129674. doi: 10.1016/j.ijbiomac.2024.129674. Epub 2024 Jan 26.
The pro-tumorigenic M2-type tumor-associated macrophages (TAMs) in the immunosuppressive tumor microenvironment (TME) promote the progression, angiogenesis, and metastasis of breast cancer. The repolarization of TAMs from an M2-type toward an M1-type holds great potential for the inhibition of breast cancer. Here, we report that Lycium barbarum polysaccharides (LBPs) can significantly reconstruct the TME by modulating the function of TAMs. Specifically, we separated four distinct molecular weight segments of LBPs and compared their repolarization effects on TAMs in TME. The results showed that LBP segments within 50-100 kDa molecular weight range exhibited the prime effect on the macrophage repolarization, augmented phagocytosis effect of the repolarized macrophages on breast cancer cells, and regression of breast tumor in a tumor-bearing mouse model. In addition, RNA-sequencing confirms that this segment of LBP displays an enhanced anti-breast cancer effect through innate immune responses. This study highlights the therapeutic potential of LBP segments within the 50-100 kDa molecular weight range for macrophage repolarization, paving ways to offer new strategies for the treatment of breast cancer.
免疫抑制性肿瘤微环境（TME）中具有促肿瘤作用的M2型肿瘤相关巨噬细胞（TAM）会促进乳腺癌的进展、血管生成和转移。将TAM从M2型重新极化至M1型在抑制乳腺癌方面具有巨大潜力。在此，我们报告枸杞多糖（LBP）可通过调节TAM的功能显著重建TME。具体而言，我们分离出LBP的四个不同分子量片段，并比较了它们对TME中TAM的重新极化作用。结果表明，分子量范围在50 - 100 kDa的LBP片段对巨噬细胞重新极化具有主要作用，增强了重新极化后的巨噬细胞对乳腺癌细胞的吞噬作用，并使荷瘤小鼠模型中的乳腺肿瘤消退。此外，RNA测序证实该片段的LBP通过先天免疫反应显示出增强的抗乳腺癌作用。本研究突出了分子量范围在50 - 100 kDa的LBP片段在巨噬细胞重新极化方面的治疗潜力，为乳腺癌治疗提供新策略开辟了道路。
