ArticlePloS one2015
Tumor-Associated Endothelial Cells Promote Tumor Metastasis by Chaperoning Circulating Tumor Cells and Protecting Them from Anoikis.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
45 citing papers in PubMed, 67 citations in OpenAlex.
- IGFBP5 derived from endothelial cells drive vascular invasion and liver metastasis of colorectal cancer by activating the ITGB3/PI3K/AKT Axis.Cell death & disease · 2026Article
- Cancer stem cell plasticity: mechanisms, immune microenvironment crosstalk, and therapeutic implications.Journal of hematology & oncology · 2026Review
- Endothelial cell-specific DNA methylation alterations in breast cancer.Communications biology · 2026Article
- Development of a high-throughput TR-FRET assay to identify inhibitors of the FAK-paxillin protein-protein interaction.SLAS discovery : advancing life sciences R & D · 2025Article
- Circulating Tumor Microenvironment in Metastasis.Cancer research · 2025Review
- Targeting Cancer: Microenvironment and Immunotherapy Innovations.International journal of molecular sciences · 2024Review
- Current biological implications and clinical relevance of metastatic circulating tumor cells.Clinical and experimental medicine · 2024Review
- Nasopharyngeal carcinoma: current views on the tumor microenvironment's impact on drug resistance and clinical outcomes.Molecular cancer · 2024Review
- Endothelial cells in tumor microenvironment: insights and perspectives.Frontiers in immunology · 2024Review
- The Prognosis of Cancer Depends on the Interplay of Autophagy, Apoptosis, and Anoikis within the Tumor Microenvironment.Cell biochemistry and biophysics · 2023Review
- Insights into N6-methyladenosine (m6A) modification of noncoding RNA in tumor microenvironment.Aging · 2023Review
- Review
- Review
- Crosstalk between N6-methyladenosine (m6A) modification and noncoding RNA in tumor microenvironment.International journal of biological sciences · 2023Review
- Tumour associated endothelial cells: origin, characteristics and role in metastasis and anti-angiogenic resistance.Frontiers in physiology · 2023Review
- Targeting the tumor stroma for cancer therapy.Molecular cancer · 2022Review
- Review
- Mitochondria dysfunction in circulating tumor cells.Frontiers in oncology · 2022Review
- The tumor microenvironment as driver of stemness and therapeutic resistance in breast cancer: New challenges and therapeutic opportunities.Cellular oncology (Dordrecht, Netherlands) · 2021Review
- Circulating Tumour Cells (CTCs) in NSCLC: From Prognosis to Therapy Design.Pharmaceutics · 2021Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Tumor metastasis is a highly inefficient biological process as millions of tumor cells are released in circulation each day and only a few of them are able to successfully form distal metastatic nodules. This could be due to the fact that most of the epithelial origin cancer cells are anchorage-dependent and undergo rapid anoikis in harsh circulating conditions. A number of studies have shown that in addition to tumor cells, activated endothelial cells are also released into the blood circulation from the primary tumors. However, the precise role of these activated circulating endothelial cells (CECs) in tumor metastasis process is not known. Therefore, we performed a series of experiments to examine if CECs promoted tumor metastasis by chaperoning the tumor cells to distal sites. Our results demonstrate that blood samples from head and neck cancer patients contain significantly higher Bcl-2-positive CECs as compared to healthy volunteers. Technically, it is challenging to know the origin of CECs in patient blood samples, therefore we used an orthotopic SCID mouse model and co-implanted GFP-labeled endothelial cells along with tumor cells. Our results suggest that activated CECs (Bcl-2-positive) were released from primary tumors and they co-migrated with tumor cells to distal sites. Bcl-2 overexpression in endothelial cells (EC-Bcl-2) significantly enhanced adhesion molecule expression and tumor cell binding that was predominantly mediated by E-selectin. In addition, tumor cells bound to EC-Bcl-2 showed a significantly higher anoikis resistance via the activation of Src-FAK pathway. In our in vivo experiments, we observed significantly higher lung metastasis when tumor cells were co-injected with EC-Bcl-2 as compared to EC-VC. E-selectin knockdown in EC-Bcl-2 cells or FAK/FUT3 knockdown in tumor cells significantly reversed EC-Bcl-2-mediated tumor metastasis. Taken together, our results suggest a novel role for CECs in protecting the tumor cells in circulation and chaperoning them to distal sites.
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