髓膜下转移（LM）是指肿瘤细胞扩散到围绕脑和脊髓的髓膜空间，导致临床结果不佳。三阴性乳腺癌（TNBC）与LM的症状有关，然而其机制尚不清楚。通过蛋白质组学分析，我们发现，在髓膜转移性TNBC细胞中，ICAM2的表达高，这促进了脊髓的定居，导致体内存活率不佳。双向验证表明，ICAM2水平的升高促进了血脑脊液屏障（BCB）的粘附、跨越BCB的迁移，并决定了体内LM的特异性。此外，拉取-下来法和抗体中和实验揭示，ICAM2通过与脉络丛上皮细胞的ICAM1相互作用来决定LM的特异性。因此，中和ICAM2可以减轻LM的进展，并延长体内存活。研究结果表明，定位ICAM2可能是治疗TNBC中LM的潜在策略。© 2023. The Author(s).

Leptomeningeal metastasis (LM) occurs when tumor cells spread to the leptomeningeal space surrounding the brain and the spinal cord, thereby causing poor clinical outcomes. The triple-negative breast cancer (TNBC) has been associated with symptoms of LM and mechanism remained unclear. Through proteomic analysis, we identified high expression of ICAM2 in leptomeningeal metastatic TNBC cells, which promoted the colonization of the spinal cord and resulted in poor survival in vivo. Two-way demonstration indicated that high levels of ICAM2 promoted blood-cerebrospinal fluid barrier (BCB) adhesion, trans-BCB migration, and stemness abilities and determined the specificity of LM in vivo. Furthermore, pull-down and antibody neutralizing assay revealed that ICAM2 determined the specificity of LM through interactions with ICAM1 in the choroid plexus epithelial cells. Therefore, neutralizing ICAM2 can attenuate the progression of LM and prolong survival in vivo. The results suggested that targeting ICAM2 is a potential therapeutic strategy for LM in TNBC.© 2023. The Author(s).