ArticleOncogene2017
Blood vessel endothelium-directed tumor cell streaming in breast tumors requires the HGF/C-Met signaling pathway.
Article in Oncogene, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 97 citations in OpenAlex.
- Evolving roles of MET as a therapeutic target in NSCLC and beyond.Nature reviews. Clinical oncology · 2025Review
- Targeting CSF-1 signaling between tumor cells and macrophages at TMEM doorways inhibits breast cancer dissemination.Oncogene · 2025Article
- Review
- Spatio-Temporal Dynamics of MBulletin of mathematical biology · 2025Article
- Reciprocal Modulation of Tumour and Immune Cell Motility: Uncovering Dynamic Interplays and Therapeutic Approaches.Cancers · 2025Review
- Decoding tumor angiogenesis: pathways, mechanisms, and future directions in anti-cancer strategies.Biomarker research · 2025Review
- Visualizing cellular interactions: intravital imaging in tumor microenvironment.Frontiers in immunology · 2025Review
- Tumor-neutrophil cross talk orchestrates the tumor microenvironment to determine the bladder cancer progression.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Signaling events at TMEM doorways provide potential targets for inhibiting breast cancer dissemination.bioRxiv : the preprint server for biology · 2024Article
- Phenotypic Heterogeneity, Bidirectionality, Universal Cues, Plasticity, Mechanics, and the Tumor Microenvironment Drive Cancer Metastasis.Biomolecules · 2024Review
- Macrophages in tumor cell migration and metastasis.Frontiers in immunology · 2024Review
- TCAF2 in Pericytes Promotes Colorectal Cancer Liver Metastasis via Inhibiting Cold-Sensing TRPM8 Channel.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Angiogenic signaling pathways and anti-angiogenic therapy for cancer.Signal transduction and targeted therapy · 2023Review
- Multidimensional Imaging of Breast Cancer.Cold Spring Harbor perspectives in medicine · 2023Review
- Cooperative NF-κB and Notch1 signaling promotes macrophage-mediated MenaINV expression in breast cancer.Breast cancer research : BCR · 2023Article
- Menstrual blood-derived stromal cells: insights into their secretome in acute hypoxia conditions.Molecular medicine (Cambridge, Mass.) · 2023Article
- Macrophages Promote Tumor Cell Extravasation across an Endothelial Barrier through Thin Membranous Connections.Cancers · 2023Article
- Interaction of tumor‑associated macrophages with stromal and immune components in solid tumors: Research progress (Review).International journal of oncology · 2023Review
- Intravital imaging to study cancer progression and metastasis.Nature reviews. Cancer · 2023Review
- Proteolytic and mechanical remodeling of the extracellular matrix by invadopodia in cancer.Physical biology · 2022Review
1 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
During metastasis to distant sites, tumor cells migrate to blood vessels. In vivo, breast tumor cells utilize a specialized mode of migration known as streaming, where a linear assembly of tumor cells migrate directionally towards blood vessels on fibronectin-collagen I-containing extracellular matrix (ECM) fibers in response to chemotactic signals. We have successfully reconstructed tumor cell streaming in vitro by co-plating tumors cells, macrophages and endothelial cells on 2.5 μm thick ECM-coated micro-patterned substrates. We found that tumor cells and macrophages, when plated together on the micro-patterned substrates, do not demonstrate sustained directional migration in only one direction (sustained directionality) but show random bi-directional walking. Sustained directionality of tumor cells as seen in vivo was established in vitro when beads coated with human umbilical vein endothelial cells were placed at one end of the micro-patterned 'ECM fibers' within the assay. We demonstrated that these endothelial cells supply the hepatocyte growth factor (HGF) required for the chemotactic gradient responsible for sustained directionality. Using this in vitro reconstituted streaming system, we found that directional streaming is dependent on, and most effectively blocked, by inhibiting the HGF/C-Met signaling pathway between endothelial cells and tumor cells. Key observations made with the in vitro reconstituted system implicating C-Met signaling were confirmed in vivo in mammary tumors using the in vivo invasion assay and intravital multiphoton imaging of tumor cell streaming. These results establish HGF/C-Met as a central organizing signal in blood vessel-directed tumor cell migration in vivo and highlight a promising role for C-Met inhibitors in blocking tumor cell streaming and metastasis in vivo, and for use in human trials.
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