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Review Open Access

Platelet‑circulating tumor cell crosstalk: A pivotal target in cancer diagnosis and therapy (Review)

  • Authors:
    • Lifang Zhang
    • Ye Yuan
    • Yan Deng
    • Lin Wang
    • Fenghua Chen
  • View Affiliations / Copyright

    Affiliations: Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China, Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
    Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 2
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    Published online on: October 15, 2025
       https://doi.org/10.3892/or.2025.9007
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Abstract

Platelets, while essential for hemostasis, have been recognized as critical mediators in cancer metastasis. The crosstalk between platelets and circulating tumor cells (CTCs) constitutes a key driver of metastasis, emerging as a focal point in oncology research. Elucidating the underlying mechanisms provides novel insights into tumor dissemination. The present review systematically traces the evolution of platelet‑CTC crosstalk, from receptor‑mediated adhesion to bidirectional molecular exchange, and its implications for metastatic progression. Additionally, the diagnostic significance of platelet‑CTC complexes as potential biomarkers for cancer detection and prognosis is highlighted. Finally, promising therapeutic strategies targeting the platelet‑CTC crosstalk are discussed. By integrating current knowledge, it was demonstrated that targeting platelet‑CTC crosstalk holds potential for improving cancer diagnosis and therapy, while also identifying avenues for future translational research.
View Figures

Figure 1

Historical timeline of platelet-CTC
crosstalk. The present review emphasizes contemporary advancements
in platelet-CTC crosstalk, with its historical progression
illustrated in the figure. CTC, circulating tumor cell. Created
with Adobe Illustrator 2020.

Figure 2

Receptor pairs governing platelet-CTC
crosstalk. The depicted molecular interactions encompass: CLEC-2
(platelets) binding to podoplanin (cancer cells); GP Ib-IX–V
complex (platelets) interacting with vWF (cancer cells); GPIIb/IIIa
(αIIbβ3 integrin) (platelets) binding to ligands such as fibrinogen
and vWF; GPVI (platelets) recognizing galectin-3, collagen, and
fibrin on cancer cells; integrin αvβ3 (cancer cells) engaging RGD
motifs; PAR (cancer cells) mediating thrombin-dependent platelet
activation; integrin α6β1 (platelets) binding to ADAM9 (cancer
cell); platelet-derived Asm inducing p38K phosphorylation and
integrin α5β1 activation in tumor cells; P-selectin (platelets)
interacting with sLex and mucins on cancer cells. These
receptor-ligand engagements collectively enhance platelet adhesion
to CTCs, facilitating vascular retention, extravasation and
metastatic dissemination. CTC, circulating tumor cell; GP,
glycoprotein; vWF, von Willebrand factor; RGD, Arg-Gly-Asp
sequence; Asm, acidic sphingomyelinase; SLex, sialyl
Lewisx; PAR, protease-activated receptor. Created with
Adobe Illustrator 2020.

Figure 3

Bidirectional interactions between
platelets and CTCs. (A) Platelet-mediated tumor promotion: i)
Platelets create a protective shield around CTCs, safeguarding them
from fluid shear stress and immune attack. ii) Platelet surface
receptors enhance cancer cell adhesion and vascular retention. iii)
Platelet-derived LPA binds to LPA receptor 1 on cancer cells,
promoting invasion. Platelet-released ATP interacts with
endothelial P2Y2 receptors to facilitate CTC
extravasation. (B) Tumor-mediated platelet modulation: i) Platelets
uptake and enrich tumor-specific biomolecules, leading to altered
DNA/RNA/protein expression profiles characteristic of
tumor-educated platelets. ii) Tumor-secreted TPO or IL-6 stimulates
megakaryopoiesis and thrombopoiesis in bone marrow, resulting in
thrombocytosis. iii) Tumor cells activate platelets and induce
their aggregation. CTC, circulating tumor cell; ATP, adenosine
triphosphate; LPA, lysophosphatidic acid; IL-6, interleukin-6; TPO,
thrombopoietin. Created with Adobe Illustrator 2020.

Figure 4

Five strategies of engineered
platelet technology. (A) Drug-loaded platelets are prepared through
co-incubation of DOX with platelets, subsequently targeting CTCs
via ‘tumor cell-induced platelet aggregation’ and releasing DOX.
(B) Following platelet activation, EVs are released, purified by
centrifugation and filtration, and subsequently loaded with DOX.
The resulting drug-carrying EVs adhere to CTCs and release DOX
within the bloodstream. (C) Drugs are loaded onto platelets via
surface modification, and drug-loaded microparticles are released
upon platelet activation. (D) Megakaryocytes are genetically
engineered to differentiate into tumor-resistant platelets. (E)
Membrane-derived vesicles are generated from platelets using
repeated freeze-thaw cycles and ultrasonication. The purified
vesicles encapsulate nanoparticles via electrostatic interactions.
This approach combines platelet engineering with nanotechnology.
DOX, doxorubicin; CTCs, circulating tumor cells; EVs, extracellular
vesicles. Created with Adobe Illustrator 2020.
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Copy and paste a formatted citation
Spandidos Publications style
Zhang L, Yuan Y, Deng Y, Wang L and Chen F: Platelet‑circulating tumor cell crosstalk: A pivotal target in cancer diagnosis and therapy (Review). Oncol Rep 55: 2, 2026.
APA
Zhang, L., Yuan, Y., Deng, Y., Wang, L., & Chen, F. (2026). Platelet‑circulating tumor cell crosstalk: A pivotal target in cancer diagnosis and therapy (Review). Oncology Reports, 55, 2. https://doi.org/10.3892/or.2025.9007
MLA
Zhang, L., Yuan, Y., Deng, Y., Wang, L., Chen, F."Platelet‑circulating tumor cell crosstalk: A pivotal target in cancer diagnosis and therapy (Review)". Oncology Reports 55.1 (2026): 2.
Chicago
Zhang, L., Yuan, Y., Deng, Y., Wang, L., Chen, F."Platelet‑circulating tumor cell crosstalk: A pivotal target in cancer diagnosis and therapy (Review)". Oncology Reports 55, no. 1 (2026): 2. https://doi.org/10.3892/or.2025.9007
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang L, Yuan Y, Deng Y, Wang L and Chen F: Platelet‑circulating tumor cell crosstalk: A pivotal target in cancer diagnosis and therapy (Review). Oncol Rep 55: 2, 2026.
APA
Zhang, L., Yuan, Y., Deng, Y., Wang, L., & Chen, F. (2026). Platelet‑circulating tumor cell crosstalk: A pivotal target in cancer diagnosis and therapy (Review). Oncology Reports, 55, 2. https://doi.org/10.3892/or.2025.9007
MLA
Zhang, L., Yuan, Y., Deng, Y., Wang, L., Chen, F."Platelet‑circulating tumor cell crosstalk: A pivotal target in cancer diagnosis and therapy (Review)". Oncology Reports 55.1 (2026): 2.
Chicago
Zhang, L., Yuan, Y., Deng, Y., Wang, L., Chen, F."Platelet‑circulating tumor cell crosstalk: A pivotal target in cancer diagnosis and therapy (Review)". Oncology Reports 55, no. 1 (2026): 2. https://doi.org/10.3892/or.2025.9007
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