Biomaterial Scaffolds as Pre-metastatic Niche Mimics Systemically Alter the Primary Tumor and Tumor Microenvironment.
Biomaterial Scaffolds as Pre-metastatic Niche Mimics Systemically Alter the Primary Tumor and Tumor Microenvironment.
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DOI：
10.1002/adhm.201700903
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发表时间：
2018-05
影响因子：
10
通讯作者：
Shea LD
中科院分区：
文献类型：
--
作者：
Aguado BA;Hartfield RM;Bushnell GG;Decker JT;Azarin SM;Nanavati D;Schipma MJ;Rao SS;Oakes RS;Zhang Y;Jeruss JS;Shea LD
原发肿瘤(PT)免疫细胞和转移前壁龛(PMN)是转移的关键。最近，作为PMN模拟物的合成生物材料支架被证明可以捕获免疫和转移肿瘤细胞。本研究旨在探讨支架介导的免疫和肿瘤细胞重定向是否会改变原发肿瘤微环境(TME)。对植入支架和模拟手术的小鼠的PT细胞进行转录转录分析，确定与侵袭和转移进展相关的不同调控途径。转录差异被认为是支架介导的免疫细胞运输和TME表型调控的结果。用支架植入小鼠的PT免疫细胞产生的条件培养液培养肿瘤细胞，与模拟手术对照组相比，体外侵袭减少两倍以上，并降低侵袭促进转录因子的活性。条件培养液的分泌学特征描述了TME中免疫细胞和肿瘤细胞之间的相互作用，显示泛转移抑制因子Decorin增加，伴随而来的是支架植入小鼠侵袭促进趋化因子(C-C基序)配体2(CCL2)的减少。流式细胞术和PT免疫细胞转录谱分析在支架植入的小鼠中识别出表型独特的肿瘤相关巨噬细胞(TAM)，这可能有助于抑制侵袭的TME。综上所述，这项研究表明，生物材料支架通过操纵TME系统地影响转移进展。
Primary tumor (PT) immune cells and pre-metastatic niche (PMN) sites are critical to metastasis. Recently, synthetic biomaterial scaffolds used as PMN mimics are shown to capture both immune and metastatic tumor cells. Herein, studies are performed to investigate whether the scaffold-mediated redirection of immune and tumor cells would alter the primary tumor microenvironment (TME). Transcriptomic analysis of PT cells from scaffold-implanted and mock-surgery mice identifies differentially regulated pathways relevant to invasion and metastasis progression. Transcriptomic differences are hypothesized to result from scaffold-mediated modulations of immune cell trafficking and phenotype in the TME. Culturing tumor cells with conditioned media generated from PT immune cells of scaffold-implanted mice decrease invasion in vitro more than two-fold relative to mock surgery controls and reduce activity of invasion-promoting transcription factors. Secretomic characterization of the conditioned media delineates interactions between immune cells in the TME and tumor cells, showing an increase in the pan-metastasis inhibitor decorin and a concomitant decrease in invasion-promoting chemokine (C-C motif) ligand 2 (CCL2) in scaffold-implanted mice. Flow cytometric and transcriptomic profiling of PT immune cells identify phenotypically distinct tumor-associated macrophages (TAMs) in scaffold-implanted mice, which may contribute to an invasion-suppressive TME. Taken together, this study demonstrates biomaterial scaffolds systemically influence metastatic progression through manipulation of the TME.
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DOI：
10.1083/jcb.201507018
发表时间：
2016-02-15
期刊：
The Journal of cell biology
影响因子：
--
作者：
Dubash AD;Kam CY;Aguado BA;Patel DM;Delmar M;Shea LD;Green KJ
通讯作者：
Green KJ
影响因子：
3.5
作者：
Araki, Kentaro;Wakabayashi, Hiroki;Uchida, Atsumasa
通讯作者：
Uchida, Atsumasa
影响因子：
4.8
作者：
Fang, Wei Bin;Jokar, Iman;Cheng, Nikki
通讯作者：
Cheng, Nikki
肿瘤相关巨噬细胞的细胞和分子起源。
DOI：
10.1126/science.1252510
发表时间：
2014-05-23
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Franklin RA;Liao W;Sarkar A;Kim MV;Bivona MR;Liu K;Pamer EG;Li MO
通讯作者：
Li MO
影响因子：
19
作者：
Ell, Brian;Kang, Yibin
通讯作者：
Kang, Yibin