ArticleProceedings of the National Academy of Sciences of the United States of America2018
Inflamed neutrophils sequestered at entrapped tumor cells via chemotactic confinement promote tumor cell extravasation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 119 papers.
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Who cites it
119 citing papers in PubMed.
- Leveraging Microphysiological Systems to Facilitate Neutrophil-Based Cancer Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Platelet-neutrophil cooperation in cancer: mechanisms of metastatic niche formation and implications for prognostic stratification and therapy.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Neutrophil extracellular traps in the tumor microenvironment, metastasis, therapy, and beyond: advances, challenges, and perspectives.Journal of hematology & oncology · 2026Review
- Quantifying the Dual Effect of Antitumor and Pro-Tumor Human Neutrophils on Natural Killer Cell Behaviors in a Microphysiological System.ACS biomaterials science & engineering · 2026Article
- Dexamethasone promotes neutrophil ROS-mediated tumor killing through the glucocorticoid receptor.Oncogene · 2026Article
- Applying microfluidic technology to interpret the tumor immune microenvironment and cancer immunotherapy.Cancer biology & medicine · 2026Review
- Spatiotemporal dynamics of tumor-associated neutrophils: bridging the gap between cancer progression and immunotherapy.Molecular cancer · 2026Review
- Microphysiological systems for metastasis research: a stepwise approach.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- High-Throughput 3D Bioprinted Organoids of Skin Cancer Utilized for Diagnosis and Personalized Therapy.Current oncology (Toronto, Ont.) · 2025Review
- Detection of Circulating Cancer-Associated Fibroblasts in Head and Neck Squamous Cell Carcinoma and Their Impact on Circulating Tumor Cells.Head & neck · 2025Article
- Endothelial activation during the diapedesis of cancer cells: between the kiss of death and therapeutic breakthrough.Cellular & molecular biology letters · 2025Review
- A microfluidic platform for the co-culturing of microtissues with continuously recirculating suspension cells.Microsystems & nanoengineering · 2025Article
- The Duality of Collagens in Metastases of Solid Tumors.International journal of molecular sciences · 2025Review
- GABAergic signaling contributes to tumor cell invasion and poor overall survival in colorectal cancer.Oncogene · 2025Article
- The Interleukin-8-CXCR1/2 Axis as a Therapeutic Target in Peritoneal Carcinomatosis.Current oncology (Toronto, Ont.) · 2025Review
- Cancer-on-a-chip for precision cancer medicine.Lab on a chip · 2025Review
- A Web of Challenges: The Therapeutic Struggle to Target NETs in Disease.International journal of molecular sciences · 2025Review
- A Biomimetic Human Multi-Cellular In Vitro Model of the Blood-Brain Barrier.International journal of molecular sciences · 2025Article
- Molecular Underpinnings of Brain Metastases.International journal of molecular sciences · 2025Review
- Tubulin-Based Microtentacles Aid in Heterotypic Clustering of Neutrophil-Differentiated HL-60 Cells and Breast Tumor Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
59 more citing papers are in PubMed but not listed here.
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7 authors.
Funding
Abstract
Systemic inflammation occurring around the course of tumor progression and treatment are often correlated with adverse oncological outcomes. As such, it is suspected that neutrophils, the first line of defense against infection, may play important roles in linking inflammation and metastatic seeding. To decipher the dynamic roles of inflamed neutrophils during hematogenous dissemination, we employ a multiplexed microfluidic model of the human microvasculature enabling physiologically relevant transport of circulating cells combined with real-time, high spatial resolution observation of heterotypic cell-cell interactions. LPS-stimulated neutrophils (PMNs) and tumor cells (TCs) form heterotypic aggregates under flow, and arrest due to both mechanical trapping and neutrophil-endothelial adhesions. Surprisingly, PMNs are not static following aggregation, but exhibit a confined migration pattern near TC-PMN clusters. We discover that PMNs are chemotactically confined by self-secreted IL-8 and tumor-derived CXCL-1, which are immobilized by the endothelial glycocalyx. This results in significant neutrophil sequestration with arrested tumor cells, leading to the spatial localization of neutrophil-derived IL-8, which also contributes to increasing the extravasation potential of adjacent tumor cells through modulation of the endothelial barrier. Strikingly similar migration patterns and extravasation behaviors were also observed in an in vivo zebrafish model upon PMN-tumor cell coinjection into the embryo vasculature. These insights into the temporal dynamics of intravascular tumor-PMN interactions elucidate the mechanisms through which inflamed neutrophils can exert proextravasation effects at the distant metastatic site.
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