ArticleExperimental hematology & oncology2024
Targeting SPP1-orchestrated neutrophil extracellular traps-dominant pre-metastatic niche reduced HCC lung metastasis.
Article in Experimental hematology & oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed.
- Niches in cancer: from primary tumors to metastatic disease.Journal of hematology & oncology · 2026Review
- Metabolic reprogramming in cancer-associated fibroblasts: orchestrating the tumor immune microenvironment and response to immune checkpoint blockade.Experimental hematology & oncology · 2026Review
- From Gut Microbiota to Hepatic Pre-Metastatic Niches: Mechanism and Translational Prospects of the Gut-Liver Axis in Regulating Colorectal Cancer Liver Metastasis.Microorganisms · 2026Review
- Hepatocellular carcinoma metastasis-immune microenvironment crosstalk: emerging mechanisms and immunotherapy.Cellular & molecular biology letters · 2026Review
- Roles of neutrophil extracellular traps in cancer immunotherapy resistance and therapeutic targeting.Biomarker research · 2026Review
- Non-invasive model for predicting future lung metastasis of hepatocellular carcinoma based on imaging heterogeneity analysis.Cancer imaging : the official publication of the International Cancer Imaging Society · 2026Article
- Bidirectional crosstalk between cancer-associated fibroblasts and tumor immunity: shaping the microenvironment and response to immune checkpoint therapy.Experimental hematology & oncology · 2026Review
- SPP1Cell death & disease · 2026Article
- Neutrophil extracellular traps in the tumor microenvironment, metastasis, therapy, and beyond: advances, challenges, and perspectives.Journal of hematology & oncology · 2026Review
- ETV7 promotes 5-FU resistance and malignant progression through CXCL1-induced NETs formation in colorectal cancer.Communications biology · 2026Article
- The pre-metastatic niche: mechanisms, heterogeneity, and therapeutic opportunities.Molecular cancer · 2026Review
- CXCL1-overexpressing cancer-associated fibroblasts stimulate hepatocellular carcinoma progression via neutrophil recruitment, NET formation, and immune suppression.Cancer immunology, immunotherapy : CII · 2026Article
- Neutrophil Extracellular Traps in Cancer Metastasis: From Mechanistic Understanding to Targeted Therapy.Current oncology (Toronto, Ont.) · 2026Review
- A pathology-to-single-cell framework links SPP1Journal of translational medicine · 2026Article
- The Molecular Network of Neutrophil Extracellular Traps in Hepatocellular Carcinoma: Biogenesis, Function, and Therapeutic Implications.Molecules (Basel, Switzerland) · 2026Review
- Integrated single-cell and bulk RNA sequencing unravels neutrophil heterogeneity and validates SPP1 as a prognostic biomarker in cervical cancer.BMC cancer · 2026Article
- Sivelestat sodium mitigates lung injury post-acute pulmonary embolism by inhibiting NE-SPP1 neutrophil recruitment and restoring redox balance.Scientific reports · 2026Article
- Piroxicam accelerates diabetic foot ulcer healing via ERα-dependent mitochondrial protection and oxidative stress relief.Frontiers in pharmacology · 2026Article
- Lapatinib Promotes Apoptosis in Hepatoma Cells by Regulating SPP1 Expression.Anti-cancer agents in medicinal chemistry · 2026Article
- The metastasis landscape ofFrontiers in immunology · 2026Article
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Abstract
backgroundThe mechanisms by which tumor-derived factors remodel the microenvironment of target organs to facilitate cancer metastasis, especially organ-specific metastasis, remains obscure. Our previous studies have demonstrated that SPP1 plays a key role in promoting metastasis of hepatocellular carcinoma (HCC). However, the functional roles and mechanisms of tumor-derived SPP1 in shaping the pre-metastatic niche (PMN) and promoting lung-specific metastasis are unclear.
methodsOrthotopic metastasis models, experimental metastasis models, CyTOF and flow cytometry were conducted to explore the function of SPP1 in shaping neutrophil-dominant PMN and promoting HCC lung metastasis. The main source of CXCL1 in lung tissues was investigated via fluorescence activated cell sorting and immunofluorescence staining. The expression of neutrophils and neutrophil extracellular traps (NETs) markers was detected in the lung metastatic lesions of HCC patients and mouse lung specimens. The therapeutic significance was explored via in vivo DNase I and CXCR2 inhibitor assays.
resultsSPP1 promoted HCC lung colonization and metastasis by modifying pulmonary PMN in various murine models, and plasma SPP1 levels were closely associated with lung metastasis in HCC patients. Mechanistically, SPP1 binded to CD44 on lung alveolar epithelial cells to produce CXCL1, thereby attracting and forming neutrophil-abundant PMN in the lung. The recruited neutrophils were activated by SPP1 and then formed NETs-dominant PMN to trap the disseminated tumor cells and promote metastatic colonization. Moreover, early intervention of SPP1-orchestrated PMN by co-targeting the CXCL1-CXCR2 axis and NETs formation could efficiently inhibit the lung metastasis of HCC.
conclusionsOur study illustrates that HCC-lung host cell-neutrophil interactions play important roles in PMN formation and SPP1-induced HCC lung metastasis. Early intervention in SPP1-orchestrated PMN via CXCR2 inhibitor and DNase I is a potential therapeutic strategy to combat HCC lung metastasis.
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