The localization, origin, and impact of platelets in the tumor microenvironment are tumor type-dependent.

BACKGROUND: How platelets interact with and influence the tumor microenvironment (TME) remains poorly characterized. METHODS: We compared the presence and participation of platelets in the TME of two tumors characterized by highly different TME, PyMT AT-3 mammary tumors and B16F1 melanoma. RESULTS: We show that whereas firmly adherent platelets continuously line tumor vessels of both AT-3 and B16F1 tumors, abundant extravascular stromal clusters of platelets from thrombopoietin-independent origin were present only in AT-3 mammary tumors. We further show that platelets influence the angiogenic and inflammatory profiles of AT-3 and B16F1 tumors, though with very different outcomes according to tumor type. Whereas thrombocytopenia increased bleeding in both tumor types, it further caused severe endothelial degeneration associated with massive vascular leakage, tumor swelling, and increased infiltration of cytotoxic cells, only in AT-3 tumors. CONCLUSIONS: These results indicate that while platelets are integral components of solid tumors, their localization and origin in the TME, as well as their impact on its shaping, are tumor type-dependent.

Syndecan-1 Is Overexpressed in Human Thoracic Aneurysm but Is Dispensable for the Disease Progression in a Mouse Model.

Glycosaminoglycans (GAGs) pooling has long been considered as one of the histopathological characteristics defining thoracic aortic aneurysm (TAA) together with smooth muscle cells (SMCs) apoptosis and elastin fibers degradation. However, little information is known about GAGs composition or their potential implication in TAA pathology. Syndecan-1 (SDC-1) is a heparan sulfate proteoglycan that is implicated in extracellular matrix (ECM) interaction and assembly, regulation of SMCs phenotype, and various aspects of inflammation in the vascular wall. Therefore, the aim of this study was to determine whether SDC-1 expression was regulated in human TAA and to analyze its role in a mouse model of this disease. In the current work, the regulation of SDC-1 was examined in human biopsies by RT-qPCR, ELISA, and immunohistochemistry. In addition, the role of SDC-1 was evaluated in descending TAA in vivo using a mouse model combining both aortic wall weakening and hypertension. Our results showed that both SDC-1 mRNA and protein are overexpressed in the media layer of human TAA specimens. RT-qPCR experiments revealed a 3.6-fold overexpression of SDC-1 mRNA (p = 0.0024) and ELISA assays showed that SDC-1 protein was increased 2.3 times in TAA samples compared with healthy counterparts (221 ± 24 vs. 96 ± 33 pg/mg of tissue, respectively, p = 0.0012). Immunofluorescence imaging provided evidence that SMCs are the major cell type expressing SDC-1 in TAA media. Similarly, in the mouse model used, SDC-1 expression was increased in TAA specimens compared to healthy samples. Although its protective role against abdominal aneurysm has been reported, we observed that SDC-1 was dispensable for TAA prevalence or rupture. In addition, SDC-1 deficiency did not alter the extent of aortic wall dilatation, elastin degradation, collagen deposition, or leukocyte recruitment in our TAA model. These findings suggest that SDC-1 could be a biomarker revealing TAA pathology. Future investigations could uncover the underlying mechanisms leading to regulation of SDC-1 expression in TAA.

Glenzocimab does not impact glycoprotein VI-dependent inflammatory haemostasis.

Not available.

The reversed passive Arthus reaction as a model for investigating the mechanisms of inflammation-associated hemostasis.

In recent years, accumulating evidence has indicated that platelets continuously repair vascular damage at sites of inflammation and/or infection. Studies in mouse models of inflammation have highlighted the fact that the mechanisms underlying bleeding prevention by platelets in inflamed organs can substantially differ from those supporting primary hemostasis following tail tip transection or thrombus formation in models of thrombosis. As a consequence, exploration of the hemostatic function of platelets in inflammation, as well as assessment of the risk of inflammation-induced bleeding associated with a platelet deficit and/or the use of anti-thrombotic drugs, require the use of dedicated experimental models. In the present review, we present the pros and cons of the cutaneous reversed passive Arthus reaction, a model of inflammation which has been instrumental in studying how inflammation causes vascular injury and how platelets continuously intervene to repair it. The limitations and common issues encountered when working with mouse models of inflammation for investigating platelet functions in inflammation are also discussed.