Abstract
In this study, we aimed to analyse human cancer cell–platelet interactions in functional cell analyses and explore the molecular mechanisms behind tumour progression. Various functional analyses of gastric cancer (GC) cells were performed after direct/indirect co-incubation with platelets derived from GC patients. Further detailed expression and signalling analyses were performed after co-culture with direct and indirect GC cells–platelet contact. Malignant behaviours of cancer cells, such as proliferation, migration, invasion and adhesion, were significantly enhanced after direct co-incubation with platelets. Microarray analyses demonstrated changes in multiple genes, including epithelial–mesenchymal transition (EMT)-related genes. Among them, matrix metalloproteinase 9 was notably upregulated, which was validated by quantitative reverse transcription–polymerase chain reaction and western blot. Further, this change was only observed after direct co-incubation with platelets. This study demonstrated that platelets from GC patients promote malignant behaviours of GC cells through EMT-related signalling, especially by direct contact with tumour cells.
Highlights
Recent studies have elucidated that interactions of tumour cells with the surrounding tissues play pivotal roles in tumour invasion and progression.[1]
This study demonstrated that platelets from gastric cancer (GC) patients promote malignant behaviours of GC cells through epithelial–mesenchymal transition (EMT)-related signalling, especially by direct contact with tumour cells
The results of this study clearly demonstrated that platelets enhanced several malignant behaviours of GC cells
Summary
Recent studies have elucidated that interactions of tumour cells with the surrounding tissues play pivotal roles in tumour invasion and progression.[1] Other than cancer-associated fibroblasts, immune cells, one of blood cells, are considered to be deeply involved in tumour progression.[2,3] there are only a few studies about the interactions of cancer cells with platelets, even in the same blood cells. Previous experiments using laboratory animals have demonstrated that platelets play various roles in cancer, including hematogenous metastasis, the detailed mechanisms by which platelets play pro-tumorigenic roles still remain unclear.[4,5]. Our previous clinical studies indicated that intraoperative haemorrhage is more likely to develop peritoneal recurrence.[6] These findings prompted us to investigate the impact of platelets on tumour malignancy, especially concerning the development of peritoneal metastasis, by basic and clinical studies using human samples. We aimed to analyse human cancer cell–platelet interactions in functional cell analyses and explore the molecular mechanisms behind tumour progression
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