Affiliation:
1. Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan
2. National Cheng Kung University
3. National Cheng Kung University, Medical College
4. Academia Sinica
Abstract
Abstract
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, pulldown 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.
Publisher
Research Square Platform LLC
Reference40 articles.
1. Bonig L, Mohn N, Ahlbrecht J, Wurster U, Raab P, Puppe W et al. Leptomeningeal Metastasis: The Role of Cerebrospinal Fluid Diagnostics. Front Neurol 2019; 10: 839.
2. Complement Component 3 Adapts the Cerebrospinal Fluid for Leptomeningeal Metastasis;Boire A;Cell,2017
3. Leptomeningeal Carcinomatosis: A Case Report of Metastatic Triple-negative Breast Adenocarcinoma;Parker N;Cureus,2019
4. Management of Brain and Leptomeningeal Metastases from Breast Cancer;Pellerino A;Int J Mol Sci,2020
5. Clinical outcomes of leptomeningeal metastasis in patients with non-small cell lung cancer in the modern chemotherapy era;Park JH;Lung Cancer,2012