Spillane Cathy D, Cooke Niamh M, Ward Mark P, Kenny Dermot, Blackshields Gordon, Kelly Tanya, Bates Mark, Huang Yanmei, Martin Cara, Skehan Sinead, Canney Aoife, Gallagher Michael, Smyth Paul, Brady Nathan, Clarke Andres, Mohamed Bashir, Norris Lucy, Brooks Doug A, Brooks Robert D, Heatlie Jessica K, Selemidis Stavros, Hanniffy Sean, Dixon Eric, Sheils Orla, O'Toole Sharon A, O'Leary John J
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.
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.
Transl Oncol. 2021 Dec;14(12):101229. doi: 10.1016/j.tranon.2021.101229. Epub 2021 Sep 27.
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.
肿瘤转移占癌症相关死亡的90%以上。血小板是一种关键的血液成分，它促进高效转移。本研究旨在了解肿瘤 - 血小板细胞相互作用所涉及的分子机制。在代表7种癌症类型的15种上皮细胞系中检测癌细胞与血小板之间的相互作用。通过逆转录 - 聚合酶链反应（RT-PCR）对上皮 - 间质转化（EMT）相关基因和癌症干性基因进行基因表达分析。使用Affymetrix 2.0ST阵列在血小板共培养的卵巢模型上进行全转录组分析（WTA）。在所有肿瘤类型中均发生血小板黏附和激活。WTA鉴定出在血小板相互作用后，细胞运动、迁移、侵袭、黏附、发育、分化和炎症相关基因增加，而与细胞死亡和存活相关的过程减少。在一部分细胞系中也观察到侵袭能力增强。与血小板共培养的小鼠模型进行交叉比较，鉴定出5个共同改变的基因；纤溶酶原激活物抑制剂 - 1（PAI - 1）、 plekstrin同源结构域包含蛋白2（PLEK2）、5'-核苷酸酶（CD73）、腱生蛋白C（TNC）和鞘氨醇 - 1 - 磷酸脱氢酶（SDPR）。血小板与癌细胞的相互作用是驱动促转移表型的关键因素，并且似乎由5个在转移中具有既定作用的关键基因介导。靶向这些转移介质可能改善癌症患者的预后。
