Selective targeting of tumor associated macrophages in different tumor models.

Selective targeting of tumor associated macrophages in different tumor models.
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DOI:
10.1371/journal.pone.0193015
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发表时间:
2018
期刊:
影响因子:
3.7
通讯作者:
Piiper A
Piiper A
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Kakoschky B;Pleli T;Schmithals C;Zeuzem S;Brüne B;Vogl TJ;Korf HW;Weigert A;Piiper A

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肿瘤进展在很大程度上取决于交替极化(M2)肿瘤相关巨噬细胞(TAM)的存在,而经典的M1极化巨噬细胞可以促进抗肿瘤免疫反应。因此,M2-TAM的选择性抑制是高度耐药肿瘤实体如肝细胞癌(HCC)或乳腺癌中的理想抗癌方法。我们在这里检查了与M1巨噬细胞相比,选择性结合体外分化的小鼠M2巨噬细胞并被其内化的肽(称为M2 pep)是否可以用于选择性靶向肝癌和乳腺癌中的TAM。我们证实了M2 pep对体外M2极化巨噬细胞的选择性。在将悬浮的混合4 T1肿瘤细胞与M2 pep孵育后,发现大量的TAM与M2 pep相关,而在来自两种HCC小鼠模型的混合肿瘤细胞悬浮液中,M2 pep仅显示出与TAM的低度结合。M2 pep还显示出对肝巨噬细胞的低度靶向。这表明,不同肿瘤实体中的TAM显示出不同的M2 pep靶向,并且M2 pep是在含有具有显著量的迄今为止难以捉摸的M2 pep受体的M2-TAM的肿瘤实体中开发选择性M2-TAM靶向的非常有前途的方法。
Tumor progression largely depends on the presence of alternatively polarized (M2) tumor-associated macrophages (TAMs), whereas the classical M1-polarized macrophages can promote anti-tumorigenic immune responses. Thus, selective inhibition of M2-TAMs is a desirable anti-cancer approach in highly resistant tumor entities such as hepatocellular carcinoma (HCC) or breast cancer. We here examined whether a peptide that selectively binds to and is internalized by in vitro-differentiated murine M2 macrophages as compared to M1 macrophages, termed M2pep, could be used to selectively target TAMs in HCC and breast carcinoma. We confirmed selectivity of M2pep for in vitro M2 polarized macrophages. Upon incubation of suspended mixed 4T1 tumor cells with M2pep, high amounts of the TAMs were found to be associated with M2pep, whereas in mixed tumor cell suspensions from two HCC mouse models, M2pep showed only low-degree binding to TAMs. M2pep also showed low-degree targeting of liver macrophages. This indicates that the TAMs in different tumor entities show different targeting of M2pep and that M2pep is a very promising approach to develop selective M2-TAM-targeting in tumor entities containing M2-TAMs with significant amounts of the so far elusive M2pep receptor(s).
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