Translational Oncology (Dec 2021)
The induction of a mesenchymal phenotype by platelet cloaking of cancer cells is a universal phenomenon
- Cathy D. Spillane,
- Niamh M. Cooke,
- Mark P. Ward,
- Dermot Kenny,
- Gordon Blackshields,
- Tanya Kelly,
- Mark Bates,
- Yanmei Huang,
- Cara Martin,
- Sinead Skehan,
- Aoife Canney,
- Michael Gallagher,
- Paul Smyth,
- Nathan Brady,
- Andres Clarke,
- Bashir Mohamed,
- Lucy Norris,
- Doug A. Brooks,
- Robert D. Brooks,
- Jessica K. Heatlie,
- Stavros Selemidis,
- Sean Hanniffy,
- Eric Dixon,
- Orla Sheils,
- Sharon A. O'Toole,
- John J. O'Leary
Affiliations
- Cathy D. Spillane
- Department of Histopathology, Trinity College Dublin and Trinity St James's Cancer Institute, Dublin, Ireland; Emer Casey Molecular Pathology Research Laboratory, Coombe Women and Infants University Hospital, Dublin, Ireland; The Biomedical Diagnostics Institute, Dublin City University, Dublin, Ireland
- Niamh M. Cooke
- The Biomedical Diagnostics Institute, Dublin City University, Dublin, Ireland; Department of Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, 123 St Stephens Green, Dublin, Ireland
- Mark P. Ward
- Department of Histopathology, Trinity College Dublin and Trinity St James's Cancer Institute, Dublin, Ireland; Emer Casey Molecular Pathology Research Laboratory, Coombe Women and Infants University Hospital, Dublin, Ireland
- Dermot Kenny
- The Biomedical Diagnostics Institute, Dublin City University, Dublin, Ireland; Department of Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, 123 St Stephens Green, Dublin, Ireland
- Gordon Blackshields
- Department of Histopathology, Trinity College Dublin and Trinity St James's Cancer Institute, Dublin, Ireland; The Biomedical Diagnostics Institute, Dublin City University, Dublin, Ireland
- Tanya Kelly
- Department of Histopathology, Trinity College Dublin and Trinity St James's Cancer Institute, Dublin, Ireland; Emer Casey Molecular Pathology Research Laboratory, Coombe Women and Infants University Hospital, Dublin, Ireland
- Mark Bates
- Department of Histopathology, Trinity College Dublin and Trinity St James's Cancer Institute, Dublin, Ireland; Emer Casey Molecular Pathology Research Laboratory, Coombe Women and Infants University Hospital, Dublin, Ireland
- Yanmei Huang
- Department of Histopathology, Trinity College Dublin and Trinity St James's Cancer Institute, Dublin, Ireland; Emer Casey Molecular Pathology Research Laboratory, Coombe Women and Infants University Hospital, Dublin, Ireland; School of Forensic Medicine, Xinxiang Medical University, Xinxiang, Henan, China
- Cara Martin
- Department of Histopathology, Trinity College Dublin and Trinity St James's Cancer Institute, Dublin, Ireland; Emer Casey Molecular Pathology Research Laboratory, Coombe Women and Infants University Hospital, Dublin, Ireland
- Sinead Skehan
- Department of Histopathology, Trinity College Dublin and Trinity St James's Cancer Institute, Dublin, Ireland; Emer Casey Molecular Pathology Research Laboratory, Coombe Women and Infants University Hospital, Dublin, Ireland
- Aoife Canney
- Department of Histopathology, Trinity College Dublin and Trinity St James's Cancer Institute, Dublin, Ireland; Emer Casey Molecular Pathology Research Laboratory, Coombe Women and Infants University Hospital, Dublin, Ireland
- Michael Gallagher
- Department of Histopathology, Trinity College Dublin and Trinity St James's Cancer Institute, Dublin, Ireland; Emer Casey Molecular Pathology Research Laboratory, Coombe Women and Infants University Hospital, Dublin, Ireland
- Paul Smyth
- Department of Histopathology, Trinity College Dublin and Trinity St James's Cancer Institute, Dublin, Ireland
- Nathan Brady
- Department of Histopathology, Trinity College Dublin and Trinity St James's Cancer Institute, Dublin, Ireland; Emer Casey Molecular Pathology Research Laboratory, Coombe Women and Infants University Hospital, Dublin, Ireland
- Andres Clarke
- Department of Histopathology, Trinity College Dublin and Trinity St James's Cancer Institute, Dublin, Ireland; Emer Casey Molecular Pathology Research Laboratory, Coombe Women and Infants University Hospital, Dublin, Ireland
- Bashir Mohamed
- Department of Histopathology, Trinity College Dublin and Trinity St James's Cancer Institute, Dublin, Ireland; Emer Casey Molecular Pathology Research Laboratory, Coombe Women and Infants University Hospital, Dublin, Ireland
- Lucy Norris
- Department of Obstetrics and Gynaecology, Trinity College Dublin, Trinity Centre for Health Sciences, St James's Hospital, Dublin, Ireland
- Doug A. Brooks
- Department of Histopathology, Trinity College Dublin and Trinity St James's Cancer Institute, Dublin, Ireland; Cancer Research Institute, University of South Australia, Adelaide 5001, Australia
- Robert D. Brooks
- Cancer Research Institute, University of South Australia, Adelaide 5001, Australia
- Jessica K. Heatlie
- Cancer Research Institute, University of South Australia, Adelaide 5001, Australia
- Stavros Selemidis
- School of Health and Biomedical Sciences, RMIT University, Bundoora, Victoria 3083, Australia
- Sean Hanniffy
- BD Research Centre Ireland, Limerick, Ireland
- Eric Dixon
- BD Technologies and Innovation, Research Triangle Park, NC, USA
- Orla Sheils
- Department of Histopathology, Trinity College Dublin and Trinity St James's Cancer Institute, Dublin, Ireland; The Biomedical Diagnostics Institute, Dublin City University, Dublin, Ireland
- Sharon A. O'Toole
- Department of Histopathology, Trinity College Dublin and Trinity St James's Cancer Institute, Dublin, Ireland; Emer Casey Molecular Pathology Research Laboratory, Coombe Women and Infants University Hospital, Dublin, Ireland; Department of Obstetrics and Gynaecology, Trinity College Dublin, Trinity Centre for Health Sciences, St James's Hospital, Dublin, Ireland; Corresponding author at: Department of Obstetrics and Gynaecology, Trinity College Dublin, Trinity Centre for Health Sciences, St James's Hospital, Dublin, Ireland
- John J. O'Leary
- Department of Histopathology, Trinity College Dublin and Trinity St James's Cancer Institute, Dublin, Ireland; Emer Casey Molecular Pathology Research Laboratory, Coombe Women and Infants University Hospital, Dublin, Ireland; The Biomedical Diagnostics Institute, Dublin City University, Dublin, Ireland
- Journal volume & issue
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Vol. 14,
no. 12
p. 101229
Abstract
Tumour metastasis accounts for over 90% of cancer related deaths. The platelet is a key blood component, which facilitates efficient metastasis. This study aimed to understand the molecular mechanisms involved in tumour-platelet cell interactions.The interaction between cancer cells and platelets was examined in 15 epithelial cell lines, representing 7 cancer types. Gene expression analysis of EMT-associated and cancer stemness genes was performed by RT-PCR. Whole transcriptome analysis (WTA) was performed using Affymetrix 2.0ST arrays on a platelet co-cultured ovarian model.Platelet adhesion and activation occurred across all tumour types. WTA identified increases in cellular movement, migration, invasion, adhesion, development, differentiation and inflammation genes and decreases in processes associated with cell death and survival following platelet interaction. Increased invasive capacity was also observed in a subset of cell lines. A cross-comparison with a platelet co-cultured mouse model identified 5 common altered genes; PAI-1, PLEK2, CD73, TNC, and SDPR.Platelet cancer cell interactions are a key factor in driving the pro-metastatic phenotype and appear to be mediated by 5 key genes which have established roles in metastasis. Targeting these metastasis mediators could improve cancer patient outcomes.
