Margarido Andreia S, Uceda-Castro Rebeca, Hahn Kerstin, de Bruijn Roebi, Kester Lennart, Hofland Ingrid, Lohuis Jeroen, Seinstra Danielle, Broeks Annegien, Jonkers Jos, Broekman Marike L D, Wesseling Pieter, Vennin Claire, Vizoso Miguel, van Rheenen Jacco
Division of Molecular Pathology, Oncode Institute, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.
Division of Molecular Carcinogenesis, Oncode Institute, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.
Cancers (Basel). 2022 Jun 25;14(13):3115. doi: 10.3390/cancers14133115.
(1) Background: an increasing number of breast cancer patients develop lethal brain metastases (BM). The complete removal of these tumors by surgery becomes complicated when cells infiltrate into the brain parenchyma. However, little is known about the nature of these invading cells in breast cancer brain metastasis (BCBM). (2) Methods: we use intravital microscopy through a cranial window to study the behavior of invading cells in a mouse model of BCBM. (3) Results: we demonstrate that BCBM cells that escape from the metastatic mass and infiltrate into brain parenchyma undergo epithelial-to-mesenchymal transition (EMT). Moreover, cells undergoing EMT revert to an epithelial state when growing tumor masses in the brain. Lastly, through multiplex immunohistochemistry, we confirm the presence of these infiltrative cells in EMT in patient samples. (4) Conclusions: together, our data identify the critical role of EMT in the invasive behavior of BCBM, which warrants further consideration to target those cells when treating BCBM.
（1）背景：越来越多的乳腺癌患者发生致命性脑转移（BM）。当癌细胞浸润到脑实质时，通过手术完全切除这些肿瘤会变得复杂。然而，对于乳腺癌脑转移（BCBM）中这些侵袭性细胞的性质知之甚少。（2）方法：我们通过颅骨视窗利用活体显微镜来研究BCBM小鼠模型中侵袭性细胞的行为。（3）结果：我们证明，从转移瘤块中逸出并浸润到脑实质的BCBM细胞会经历上皮-间质转化（EMT）。此外，经历EMT的细胞在脑内生长肿瘤块时会恢复到上皮状态。最后，通过多重免疫组化，我们在患者样本中证实了这些处于EMT状态的浸润性细胞的存在。（4）结论：总之，我们的数据确定了EMT在BCBM侵袭行为中的关键作用，这在治疗BCBM时靶向这些细胞值得进一步考虑。
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