Direct signaling between platelets and cancer cells induces an epithelial–mesenchymal-like transition and promotes metastasis
Open accessAbstract
Interactions of cancer cells with the primary tumor microenvironment are important determinants of cancer progression toward metastasis but it is unknown whether additional prometastatic signals are provided during the intravascular transit to the site of metastasis. Here, we show that platelet-tumor cell interactions are sufficient to prime tumor cells for subsequent metastasis. Platelet-derived TGFβ and direct platelet-tumor cell contacts synergistically activate the TGFβ/Smad and NF-κB pathways in cancer cells, resulting in their transition to an invasive mesenchymal-like phenotype and enhanced metastasis in vivo. Inhibition of NF-κB signaling in cancer cells or ablation of TGFβ1 expression solely in platelets protects against lung metastasis in vivo. Thus, cancer cells rely on platelet-derived signals outside of the primary tumor for efficient metastasis.
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Neutrophils assist tumor cell extravasation following platelet aggregation around the tumor cell.
“For example, neutrophils are known to assist with tumor cell extravasation following platelet aggregation around the tumor cell[60, 61].”
From Microfluidics: A New Tool for Modeling Cancer–Immune Interactions (2016) · cites this paper as [61]
The Results section ('Platelet-Derived TGFβ1 is Necessary for Metastasis In Vivo') reports tumor cells associated with platelets in blood vessels and evidence that platelet-derived TGFβ1 aids extravasation. Neither that passage nor the Discussion passages identify neutrophils as assisting extravasation; a search for 'neutrophils' found no supporting passage. Page numbers are unavailable in our copy. (LLM, conf=0.85)
Experimental — accuracy not yet measuredThe interplay of several types of immune cells is critical for some steps of the metastatic cascade.
“Finally, future studies should analyze the role of several types of immune cells simultaneously, as their interplay has been shown to be critical for some steps of the metastatic cascade[60, 61].”
From Microfluidics: A New Tool for Modeling Cancer–Immune Interactions (2016) · cites this paper as [61]
The Introduction (page unavailable) describes platelets shielding tumor cells from natural-killer-cell lysis, and the Discussion reports that platelet–tumor-cell signaling promotes metastatic seeding. These passages support a role for cellular interactions in metastasis, but they do not establish that interplay among several types of immune cells is critical to steps of the metastatic cascade. (LLM, conf=0.78)
Experimental — accuracy not yet measuredActivated platelets activate NF-κB in cancer cells.
“Our results are also consistent with the report that activated platelets activate NF-κB in cancer cells60.”
From Platelets induce increased estrogen production through NF-κB and TGF-β1 signaling pathways in endometriotic stromal cells (2020) · cites this paper as [60]
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- Authors
- Labelle, M., Begum, S., & Hynes, R. O.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Hynes, Richard O.
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2011-11
- Volume
- 20
- Issue
- 5
- Pages
- 576-590
- ISSN
- 1535-6108 (ISSN-L)
- PMC
- PMC3487108
- OpenAlex
- W1605655296
- Cited by
- 1,833
- References
- 50
- Citations by year
- 2026: 93 · 2025: 111 · 2024: 125 · 2023: 142 · 2022: 170 · 2021: 166 · 2020: 176 · 2019: 142 · 2018: 145 · 2017: 136 · 2016: 117 · 2015: 91 · 2014: 86 · 2013: 77 · 2012: 47
- FWCI
- 28.28
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- Funders
- Howard Hughes Medical Institute
- Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology
- National Cancer Institute (U54CA163109, P30CA014051)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
- Keywords
- platelet-tumor cell interaction, metastasis, epithelial-mesenchymal transition, TGF-beta, NF-κB signaling, TGF-β/Smad signaling, lung metastasis, tumor microenvironment, tumor invasion
- MeSH terms
- Animals, Blood Platelets, Lung Neoplasms, Mice, Inbred C57BL, Molecular Sequence Data, Neoplastic Cells, Circulating, Neoplasm Invasiveness, Neoplasm Metastasis, Signal Transduction, NF-kappa B, Cell Line, Tumor, Mice, Transforming Growth Factor beta1, Epithelial-Mesenchymal Transition
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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