Prediction of tumor metastasis via extracellular vesicles-treated platelet adhesion on a blood vessel chip

In preclinical and clinical studies, it has been demonstrated that tumor-educated platelets play a critical role in tumorigenesis, cancer development, and metastasis. Unlike the role of cancer-derived chemokines in platelet activation, the role of cancer-derived extracellular vesicles (EVs) has rema...

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Bibliographic Details
Published in:Lab on a chip 2022-07, Vol.22 (14), p.2726-2740
Main Authors: Kim, Junyoung, Sunkara, Vijaya, Kim, Jungmin, Ro, Jooyoung, Kim, Chi-Ju, Clarissa, Elizabeth Maria, Jung, Sung Wook, Lee, Hee Jin, Cho, Yoon-Kyoung
Format: Article
Language:English
Subjects:
Adhesion
Blood plasma
Blood vessels
Cancer
Extracellular vesicles
Interleukins
Metastasis
Microfluidics
Performance prediction
Platelets
Tumors
Vesicles
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Summary:In preclinical and clinical studies, it has been demonstrated that tumor-educated platelets play a critical role in tumorigenesis, cancer development, and metastasis. Unlike the role of cancer-derived chemokines in platelet activation, the role of cancer-derived extracellular vesicles (EVs) has remained elusive. Here, we found that interleukin-8 (IL-8) in cancer-derived EVs contributed to platelet activation by increasing P-selectin expression and ligand affinity, resulting in increased platelet adhesion on the human vessel-mimicking microfluidic system. Furthermore, platelet adhesion levels on vessels treated with human plasma-derived EVs demonstrated good discrimination between breast cancer patients with metastasis and those without, with the area under the curve (AUC) value of 0.88. While EpCAM expression on EVs could detect the existence of a tumor (AUC = 0.89), it performed poorly in predicting metastasis (AUC = 0.42). We believe that these findings shed light on the role of the interaction between cancer-derived EVs and platelets in pre-metastatic niche formation and tumor metastasis, potentially leading to the development of platelet–tumor interaction-based novel diagnostic and therapeutic strategies.
ISSN:1473-0197
1473-0189
DOI:10.1039/d2lc00364c