Type

Journal Article

Authors

M W Radomski
C Medina
M J Santos-Martinez
D Bazou

Subjects

Medicine & Nursing

Topics
microscopy confocal ultrasonography female apyrase ultrasonics pathology metabolism platelet activation blood matrix metalloproteinase 2 blood platelets p selectin platelet glycoprotein gpiib iiia complex pharmacology physiology platelet aggregation inhibitors cell line tumor epoprostenol tumor cells cultured microscopy fluorescence actins fibrosarcoma adenocarcinoma cell communication 1 10 phenanthroline platelet aggregation phenanthrolines humans edetic acid down regulation ovarian neoplasms flow cytometry

Elucidation of flow-mediated tumour cell-induced platelet aggregation using an ultrasound standing wave trap. (2010)

Abstract Tumour cells activate and aggregate platelets [tumour cell-induced platelet aggregation (TCIPA)] and this process plays an important role in the successful metastasis of cancer cells. To date, most studies on TCIPA have been conducted under no-flow conditions. In this study, we have investigated TCIPA in real time under flow conditions, using an ultrasound standing wave trap that allows formation and levitation of cancer cell clusters in suspension, thus mimicking the conditions generated by flowing blood. Using 59M adenocarcinoma and HT1080 fibrosarcoma cells and human platelets, cancer cell cluster-platelet aggregates were imaged in real time using epi-fluorescence microscopy (F-actin) and investigated in detail using confocal microscopy (matrix metalloproteinase-2-GPIIb/IIIa co-localization) and scanning electron and helium-ion microscopy (<1 nm resolution). The release of gelatinases from aggregates was studied using zymography. We found that platelet activation and aggregation takes place on the surface of cancer cells (TCIPA), leading to time-dependent disruption of cancer cell clusters. Pharmacological modulation of TCIPA revealed that EDTA, prostacyclin, o-phenanthroline and apyrase significantly down-regulated TCIPA and, in turn, delayed cell cluster disruption, However, EGTA and aspirin were ineffective. Pharmacological inhibition of TCIPA correlated with the down-regulation of platelet activation as shown by flow-cytometry assay of platelet P-selectin. Our results show for the first time, that during TCIPA, platelet activation disrupts cancer cell clusters and this can contribute to metastasis. Thus, selective targeting of platelet aggregate-cancer cell clusters may be an important strategy to control metastasis.
Collections Ireland -> Trinity College Dublin -> PubMed

Full list of authors on original publication

M W Radomski, C Medina, M J Santos-Martinez, D Bazou

Experts in our system

1
Marek W Radomski
Trinity College Dublin
Total Publications: 44
 
2
Carlos Medina
Trinity College Dublin
Total Publications: 23
 
3
Maria Jose Santos-Martinez
Trinity College Dublin
Total Publications: 29