br By investigating the intricacies of
By investigating the intricacies of the index of platelet activation, we have identified a switched response of hormone-therapy-treated MCF7 and T47D GFT505 on P-selectin high expression (exposure), where MCF7 cells induced heightened IPA under Anastrozole treatment and T47D cells, under Tamoxifen treatment. This was further confirmed ultrastructurally. These results reflect the heterogeneous nature of platelet α-granule content, with specific release related to the eﬀects of various agonists of activation [60,61]. Tumour cells are able to secrete tumour-associated tissue factor, thrombin or ADP [7,8], thus while the levels of activation seen in our study correspond to that of the positive control (thrombin), further research is required to determine the tu-mour-secreted factors that are responsible for platelet activation in our system. Our results, which indicate Tamoxifen and Anastrozole pre-treatment increase platelet activation, substantiate clinical studies in-dicating patients are more likely to suﬀer from thromboembolic events , supporting the utilisation of targeted platelet therapies to prevent thromboembolic complications. We further highlight the diﬀerence between methodological approaches, which mirror diﬀerent aspects of the eﬀects of hormone-therapy on the tumour environment – in situ and circulatory. By using whole blood as opposed to washed platelets, we provide further evidence for the pro-thrombotic potential of Tamoxifen. In addition, this is one of the first studies investigating the eﬀects of Anastrozole pre-treatment in vitro. This emphasises the importance of investigating platelet -cancer cell interaction using diﬀerent approaches to mimic the tumour microenvironment more holistically, including a detailed assessment of the tumour phenotype on hypercoagulation.
The researchers thank the volunteers who donated blood for this study, the phlebotomist and staﬀ at the Day Ward of the Charlotte Maxeke Academic Hospital. The researchers thank the National Research Foundation of South Africa, Thuthuka Programme (NRF 87935) (TNA) and the Scarce Skills Scholarship Fund (SFH150714125894 KP).
Declaration of interest
The researchers report no conflict of interest.
 M. Kuwahara, M. Sugimoto, S. Tsuji, H. Matsui, T. Mizuno, S. Miyata, A. Yoshioka, Platelet shape changes and adhesion under high shear flow, Arterioscler. Thromb. Vasc. Biol. 22 (2) (2002) 329–334.  T.N. Augustine, W.J. van der Spuy, L.L. Kaberry, M. Shayi, Thrombin-mediated platelet activation of lysed whole blood and platelet-rich plasma: a comparison between platelet activation markers and ultrastructural alterations, Microsc. Microanal. 212 (2016).
 R.E. Rumbaut, P. Thiagarajan, Platelet‐Vessel Wall interactions in hemostasis and thrombosis, Available at: Morgan & Claypool Life Sciences, San Rafael (CA), 2010http://www.ncbi.nlm.nih.gov/books/NBK53450/.
 C.R. Meier, H. Jick, Tamoxifen and risk of idiopathic venous thromboembolism, Br.
K. Schrör, Flow cytometry analysis of platelet cyclooxygenase-2 expression: in-duction of platelet cyclooxygenase-2 in patients undergoing coronary artery bypass grafting, Br. J. Haematol. 117 (2) (2002) 424–426.
 Trappenburg MC, Schilfgaarde M Van, Marchetti M, Spronk HM, Cate H, Leyte A, Terpstra WE, Falanga A. Elevated procoagulant microparticles expressing en-dothelial and platelet markers in essential thrombocythemia. 2009;94(7):911–918. doi:https://doi.org/10.3324/haematol.13774.
 M. Walski, S. Chlopicki, R. Celary-Walska, M. Frontczak-Baniewicz, Ultrastructural alterations of endothelium covering advanced atherosclerotic plaque in human carotid artery visualised by scanning electron microscope, J. Physiol. Pharmacol. 53 (2002) 713–723.
Breast Cancer Cells Adapt Contractile Forces to Overcome Steric Hindrance
Mar Co´ndor,1,* Christoph Mark,2 Richard C. Gerum,2 Nadine C. Grummel,2 Andreas Bauer,2 Jose M. Garcı´a-Aznar,1 and Ben Fabry2
1Aragon Institute of Engineering Research, Department of Mechanical Engineering, University of Zaragoza, Zaragoza, Spain and 2Department of Physics, University of Erlangen, Erlangen, Germany
ABSTRACT Cell migration through the extracellular matrix is governed by the interplay between cell-generated propulsion forces, adhesion forces, and resisting forces arising from the steric hindrance of the matrix. Steric hindrance in turn depends on matrix porosity, matrix deformability, cell size, and cell deformability. In this study, we investigate how cells respond to changes in steric hindrance that arise from altered cell mechanical properties. Specifically, we measure traction forces, cell morphology, and invasiveness of MDA-MB 231 breast cancer cells in three-dimensional collagen gels. To modulate cell me-chanical properties, we either decrease nuclear deformability by twofold overexpression of the nuclear protein lamin A or we introduce into the cells stiff polystyrene beads with a diameter larger than the average matrix pore size. Despite this increase of steric hindrance, we find that cell invasion is only marginally inhibited, as measured by the fraction of motile cells and the mean invasion depth. To compensate for increased steric hindrance, cells employ two alternative strategies. Cells with higher nuclear stiffness increase their force polarity, whereas cells with large beads increase their net contractility. Under both condi-tions, the collagen matrix surrounding the cells stiffens dramatically and carries increased strain energy, suggesting that increased force polarity and increased net contractility are functionally equivalent strategies for overcoming an increased steric hindrance.