In vitro cross-talk between metastasis-competent circulating tumor cells and platelets in colon cancer: a malicious association during the harsh journey in the blood

Frontiers in Cell and Developmental Biology

Cell and Developmental Biology

Myron G. Best¹  Mafalda Antunes-Ferreira¹  Ilias Glogovitis¹  Silvia D’Ambrosi¹  Thomas Wurdinger¹  Keerthi Kurma²  Françoise Garima²  Catherine Alix-Panabières²  Zahra Eslami-S²  Laure Cayrefourcq²  Luis Enrique Cortés-Hernández²  Danijela Koppers-Lalic³ 

[1] Department of Neurosurgery, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Amsterdam, Netherlands;Cancer Center Amsterdam, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Amsterdam, Netherlands;Brain Tumor Center Amsterdam, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Amsterdam, Netherlands;Laboratory of Rare Circulating Human Cells—University Medical Center of Montpellier, Montpellier, France;CREEC/CANECEV, MIVEGEC (CREES), Université de Montpellier, Centre National de la Recherche Scientifique, Institut de Recherche pour le Développement, Montpellier, France;European Liquid Biopsy Society (ELBS), Hamburg, Germany;Mathematical Institute, Leiden University, Leiden, Netherlands;

关键词: platelets;    circulating tumor cells (CTCs);    epithelial-to-mesenchymal transition (EMT);    tumor-educated platelets (TEPs);    cancer;    metastasis;   

DOI  :  10.3389/fcell.2023.1209846

 received in 2023-04-21, accepted in 2023-07-24,  发布年份 2023

来源: Frontiers

【 摘 要 】

Background: Platelets are active players in hemostasis, coagulation and also tumorigenesis. The cross-talk between platelets and circulating tumor cells (CTCs) may have various pro-cancer effects, including promoting tumor growth, epithelial-mesenchymal transition (EMT), metastatic cell survival, adhesion, arrest and also pre-metastatic niche and metastasis formation. Interaction with CTCs might alter the platelet transcriptome. However, as CTCs are rare events, the cross-talk between CTCs and platelets is poorly understood. Here, we used our established colon CTC lines to investigate the colon CTC-platelet cross-talk in vitro and its impact on the behavior/phenotype of both cell types.Methods: We exposed platelets isolated from healthy donors to thrombin (positive control) or to conditioned medium from three CTC lines from one patient with colon cancer and then we monitored the morphological and protein expression changes by microscopy and flow cytometry. We then analyzed the transcriptome by RNA-sequencing of platelets indirectly (presence of a Transwell insert) co-cultured with the three CTC lines. We also quantified by reverse transcription-quantitative PCR the expression of genes related to EMT and cancer development in CTCs after direct co-culture (no Transwell insert) with platelets.Results: We observed morphological and transcriptomic changes in platelets upon exposure to CTC conditioned medium and indirect co-culture (secretome). Moreover, the expression levels of genes involved in EMT (p < 0.05) were decreased in CTCs co-cultured with platelets, but not of genes encoding mesenchymal markers (FN1 and SNAI2). The expression levels of genes involved in cancer invasiveness (MYC, VEGFB, IL33, PTGS2, and PTGER2) were increased.Conclusion: For the first time, we studied the CTC-platelet cross-talk using our unique colon CTC lines. Incubation with CTC conditioned medium led to platelet aggregation and activation, supporting the hypothesis that their interaction may contribute to preserve CTC integrity during their journey in the bloodstream. Moreover, co-culture with platelets influenced the expression of several genes involved in invasiveness and EMT maintenance in CTCs.

【 授权许可】

Unknown   
Copyright © 2023 Eslami-S, Cortés-Hernández, Glogovitis, Antunes-Ferreira, D’Ambrosi, Kurma, Garima, Cayrefourcq, Best, Koppers-Lalic, Wurdinger and Alix-Panabières.