Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.
Chemical and Biological Engineering Department, Iowa State University, Ames, IA, USA.
Nat Commun. 2023 Aug 8;14(1):4790. doi: 10.1038/s41467-023-40478-5.
Biomaterial scaffolds mimicking the environment in metastatic organs can deconstruct complex signals and facilitate the study of cancer progression and metastasis. Here we report that a subcutaneous scaffold implant in mouse models of metastatic breast cancer in female mice recruits lung-tropic circulating tumor cells yet suppresses their growth through potent in situ antitumor immunity. In contrast, the lung, the endogenous metastatic organ for these models, develops lethal metastases in aggressive breast cancer, with less aggressive tumor models developing dormant lungs suppressing tumor growth. Our study reveals multifaceted roles of neutrophils in regulating metastasis. Breast cancer-educated neutrophils infiltrate the scaffold implants and lungs, secreting the same signal to attract lung-tropic circulating tumor cells. Second, antitumor and pro-tumor neutrophils are selectively recruited to the dormant scaffolds and lungs, respectively, responding to distinct groups of chemoattractants to establish activated or suppressive immune environments that direct different fates of cancer cells.
生物材料支架模拟转移器官的环境，可以解构复杂的信号，并促进癌症进展和转移的研究。在这里，我们报告了在雌性小鼠的转移性乳腺癌小鼠模型中，皮下支架植入物招募了肺趋向性循环肿瘤细胞，但通过有效的原位抗肿瘤免疫抑制了它们的生长。相比之下，对于这些模型，肺作为内源性转移器官，在侵袭性乳腺癌中发展为致命转移，而侵袭性较小的肿瘤模型发展为休眠肺，抑制肿瘤生长。我们的研究揭示了中性粒细胞在调节转移中的多方面作用。乳腺癌诱导的中性粒细胞浸润支架植入物和肺部，分泌相同的信号吸引肺趋向性循环肿瘤细胞。其次，抗肿瘤和促肿瘤中性粒细胞分别被选择性招募到休眠支架和肺部，分别对不同的趋化因子群作出反应，建立激活或抑制免疫环境，指导癌细胞的不同命运。
