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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.
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http://dx.doi.org/10.1038/s41388-023-02769-5 | DOI Listing |
J Pharm Pharmacol
September 2025
Department of Clinical Pharmacy, Hebei Medical University Third Hospital. No. 139 Ziqiang Road, Qiaoxi District, Shijiazhuang 050051, China.
Objectives: To investigate the antitumor effects of aucubin (AC) in non-small cell lung cancer (NSCLC) and uncover its plausible mechanism against lung cancer stem-like cells (LCSCs).
Methods: In vitro experiments included MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, a reagent commonly used for cell viability assay) and colony formation assays to assess anti-proliferative effects on A549 and NCI-H1975 lung cancer cell lines, wound healing and Transwell invasion assays to evaluate inhibition of cell migration and invasion, tumorsphere-formation experiments to detect changes in NSCLC cell stemness, as well as Western blot and quantitative reverse transcription polymerase chain reaction (qRT-PCR) analyses to measure the expression of LCSC markers (CD44, CD133, Oct4, and Nanog). In vivo experiments were conducted to observe the impact of AC on NSCLC metastasis and mouse survival rates.
Research (Wash D C)
September 2025
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype, characterized by a high propensity for metastasis, poor prognosis, and limited treatment options. Research has demonstrated a substantial correlation between the expression of protein arginine N-methyltransferase 1 (PRMT1) and enhanced proliferation, metastasis, and poor outcomes in TNBC. However, the specific role of PRMT1 in lung metastasis and chemoresistance remains unclear.
View Article and Find Full Text PDFInt J Mol Sci
August 2025
Department of Pathology, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is a key regulator of cancer stem cell (CSC) biology and signaling. In CSCs, ROR1 acts as a receptor or co-receptor, interacting with non-canonical WNT ligands, and forming complexes with proteins like CD19 and HER2, to activate diverse downstream signaling pathways. ROR1 signaling in CSCs promotes proliferation, maintains stemness, and enhances migration, invasion, and the epithelial-to-mesenchymal transition (EMT).
View Article and Find Full Text PDFCancer Genomics Proteomics
August 2025
School of Medicine, Nankai University, Tianjin, P.R. China;
Background/aim: Hepatocellular carcinoma (HCC) accounts for ~90% of primary liver cancer, which ranks as the third-leading cause of global cancer mortality. Emerging evidence establishes cancer stem cells (CSCs) as central regulators of HCC progression, metastasis, and therapeutic resistance, with stemness-related pathways like Wnt/β-catenin signaling critically maintaining CSC self-renewal. In this study, we aimed to investigate the role of Peptidyl-prolyl isomerase-like 1 (PPIL1) in HCC progression and CSC self-renewal.
View Article and Find Full Text PDFCancer Med
September 2025
Department of Anatomy, Anhui Medical University, Hefei, Anhui, China.
Introduction: Pancreatic cancer (PC) is a common malignant tumor with high morbidity and mortality and a very poor prognosis, highlighting the urgent need to identify molecular therapeutic targets. Monocyte chemotactic protein-inducible protein-1 (MCPIP1) is a common inflammatory protein associated with the pathogenesis of a variety of cancers, although a comprehensive understanding of its function and the underlying mechanisms involved in PC remains unclear.
Materials And Methods: Immunohistochemistry, western blotting, immunofluorescence, flow cytometry, Transwell, and the scratch assay were used to evaluate the functional role of MCPIP1 in PC.