Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education, Chongqing Medical University, Chongqing, China.
PLoS One. 2013 Jun 25;8(6):e65896. doi: 10.1371/journal.pone.0065896. Print 2013.
Tumor-associated macrophages (TAMs) are essential cellular components within tumor microenvironment (TME). TAMs are educated by TME to transform to M2 polarized population, showing a M2-like phenotype, IL-10(high), IL-12(low), TGF-β(high). STAT3 signaling triggers crosstalk between tumor cells and TAMs, and is crucial for the regulation of malignant progression. In our study, legumain-targeting liposomal nanoparticles (NPs) encapsulating HC were employed to suppress STAT3 activity and "re-educate" TAMs, and to investigate the effects of suppression of tumor progression in vivo. The results showed that TAMs treated by HC encapsuled NPs could switch to M1-like phenotype, IL-10(low), IL-12(high), TGF-β(low), and the "re-educated" macrophages (M1-like macrophages) considerably demonstrated opposite effect of M2-like macrophages, especially the induction of 4T1 cells migration and invasion in vitro, and suppression of tumor growth, angiogenesis and metastasis in vivo. These data indicated that inhibition of STAT3 activity of TAMs by HC-NPs was able to reverse their phenotype and could regulate their crosstalk between tumor cells and TAMs in order to suppress tumor progression.
肿瘤相关巨噬细胞（TAMs）是肿瘤微环境（TME）中的重要细胞成分。TAMs 受 TME 影响而转化为 M2 极化群体，表现出 M2 样表型，IL-10（高），IL-12（低），TGF-β（高）。STAT3 信号转导触发肿瘤细胞与 TAMs 之间的串扰，对恶性进展的调控至关重要。在我们的研究中，采用靶向组织蛋白酶的脂质体纳米颗粒（NPs）包封 HC 来抑制 STAT3 活性和“重新教育”TAMs，并研究体内抑制肿瘤进展的效果。结果表明，用 HC 包封 NPs 处理的 TAMs 可转变为 M1 样表型，IL-10（低），IL-12（高），TGF-β（低），并且“重新教育”的巨噬细胞（M1 样巨噬细胞）表现出与 M2 样巨噬细胞相反的作用，特别是在体外诱导 4T1 细胞迁移和侵袭，并在体内抑制肿瘤生长，血管生成和转移。这些数据表明，HC-NPs 抑制 TAMs 的 STAT3 活性能够逆转其表型，并能够调节它们与肿瘤细胞之间的串扰，以抑制肿瘤进展。
