Single cell coagulomes as constituents of the oncogene-driven coagulant phenotype in brain tumours

Tawil, Nadim; Chennakrishnaiah, Shilpa; Bassawon, Rayhaan; Johnson, Radia Marie; D’Asti, Esterina; Rak, Janusz

doi:10.1016/j.thromres.2018.01.021

Cited by 23 publications

(21 citation statements)

References 88 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, our earlier studies revealed that the profile of coagulation-related genes is strikingly different between TCGA-designated GBM subtypes in that TF upregulation strongly correlates with EGFR expression in CL GBM, whereas both TF and PDPN are downregulated in PN tumors, which parallels their enrichment for mutant IDH1. 40,81 We have also demonstrated a direct impact of oncogenic EGFRvIII on TF expression and activity in glioma cell lines, 86 along with its biological role in GBM progression. 70,87,88 EGFRvIII also influences the levels of PAR1, FVII, and other factors.…”

Section: Oncogenic Events and Brain Tumor Coagulomementioning

confidence: 80%

“…47 For example, oncogenic RAS alters the levels of crucial angiogenic mediators such as vascular endothelial growth factor (VEGF) or thrombospondin 1, leading to the onset of vascular growth external to cancer cells. [46][47][48] The notion of oncogenic mutations being able to reprogram intercellular interactions and affect multiple facets of the cancer milieu has since been extended to other aspects such as the formation of tumor stroma, 49 recruitment of inflammatory cells, 50,51 immune responses, 52 and the state of the coagulation system, 40,[53][54][55] including CAT. 56 It should be noted that oncogenic events can contribute to CAT both directly or indirectly.…”

Section: Oncogenic Pathways As Modulators Of Vascular Responses In Camentioning

confidence: 99%

“…39 Individual tumor subtypes, patients, and cancer cell subpopulations may also exhibit different coagulant properties. 40 These changes are complex but not random. Hisada and Mackman have recently summarized the literature on several coagulant pathways that may result in CAT, all of which may differ between specific tumor types.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Oncogenes and Clotting Factors: The Emerging Role of Tumor Cell Genome and Epigenome in Cancer-Associated Thrombosis

Tawil

Bassawon

Rak

2019

Semin Thromb Hemost

Self Cite

View full text Add to dashboard Cite

There are emerging linkages between biological and genetic aspects of cancer progression and the mechanisms of cancer-associated thrombosis. It is argued that reciprocal influences between cancer cells, their associated vascular stroma, and the hemostatic system may shape the mechanism of coagulopathy. In this regard, glioblastoma multiforme offers a paradigm where the prevalent occurrence of local microthrombosis and peripheral venous thromboembolism can be linked to the profiles of oncogenic driver mutations and their impact on the expression of coagulation-related genes (coagulome). These relationships can be recapitulated in cellular models of glioblastoma, where the expression of tissue factor, podoplanin, and the release of procoagulant microparticles (extracellular vesicles) remains under the control of oncogenic pathways (epidermal growth factor receptor variant III, isocitrate dehydrogenase 1). These pathways define molecular subtypes of glioblastoma that express differential coagulomes. Moreover, single-cell sequencing of glioblastoma samples reveals a combinatorial rather than common profile of both subtype markers and coagulation-related genes. Based on these emerging observations, the authors suggest that cancers may operate as coagulant composites, where individual cells and their dominant populations express different procoagulant phenotypes, resulting in the net impact on the hemostatic system. They suggest that relating these mechanisms to clinical presentations of thrombosis may facilitate a more causality-based, personalized, and possibly cancer-specific thromboprophylaxis and treatment.

show abstract

Section: Oncogenic Events and Brain Tumor Coagulomementioning

confidence: 80%

Section: Oncogenic Pathways As Modulators Of Vascular Responses In Camentioning

confidence: 99%

See 1 more Smart Citation

Oncogenes and Clotting Factors: The Emerging Role of Tumor Cell Genome and Epigenome in Cancer-Associated Thrombosis

Tawil

Bassawon

Rak

2019

Semin Thromb Hemost

Self Cite

View full text Add to dashboard Cite

show abstract

“…For instance, oncogenic EGFR and EGFRvIII strongly upregulate tissue factor (TF) on the surface of cancer cells . TF is a transmembrane signaling receptor for coagulation factor VII/VIIa responsible for the ability of cancer cells to trigger the blood clotting cascade and cancer associated thrombosis (CAT) . CAT manifests itself as venous thromboembolism (VTE) affecting the patency of vascular beds far away from the tumor mass and is likely mediated by circulating material rather than cancer cells themselves.…”

Section: Impact Of Oncogenic Transformation On the Composition Of Thementioning

confidence: 99%

Oncogenic Regulation of Extracellular Vesicle Proteome and Heterogeneity

et al. 2019

Self Cite

View full text Add to dashboard Cite

Mutational and epigenetic driver events profoundly alter intercellular communication pathways in cancer. This effect includes deregulated release, molecular composition, and biological activity of extracellular vesicles (EVs), membranous cellular fragments ranging from a few microns to less than 100 nm in diameter and filled with bioactive molecular cargo (proteins, lipids, and nucleic acids). While EVs are usually classified on the basis of their physical properties and biogenetic mechanisms, recent analyses of their proteome suggest a larger than expected molecular diversity, a notion that is also supported by multicolour nano‐flow cytometry and other emerging technology platforms designed to analyze single EVs. Both protein composition and EV diversity are markedly altered by oncogenic transformation, epithelial to mesenchymal transition, and differentiation of cancer stem cells. Interestingly, only a subset of EVs released from mutant cells may carry oncogenic proteins (e.g., EGFRvIII), hence, these EVs are often referred to as “oncosomes”. Indeed, oncogenic transformation alters the repertoire of EV‐associated proteins, increases the presence of pro‐invasive cargo, and alters the composition of distinct EV populations. Molecular profiling of single EVs may reveal a more intricate effect of transforming events on the architecture of EV populations in cancer and shed new light on their biological role and diagnostic utility.

show abstract

“…Moreover, each GBM subtype represents a combinatorial mixture of cells with distinct coagulation profiles with enrichment of different effectors, including podoplanin (PDPN), tissue factor (TF), and other regulators. 79 This coagulant heterogeneity predicts the existence of genetically/epigenetically combinatorial CAT subtypes with different targetable mechanisms and different thrombotic severities. Protein disulfide isomerase (PDI) is an essential component of in vivo clot formation.…”

Section: Healthy Cells Cancer Cellsmentioning

confidence: 99%

Illustrated State‐of‐the‐Art Capsules of the ISTH 2019 Congress in Melbourne, Australia

Ward

Andrews

2019

Research and Practice in Thrombosis and Haemostasis

Self Cite

View full text Add to dashboard Cite

The 27th Congress of the International Society of Thrombosis and Haemostasis (ISTH) is an international conference held July 6‐10, 2019, in Melbourne, the capital of the state of Victoria, Australia. The ISTH congress has previously been held every other year, with the Scientific and Standardization Committee (SSC) meeting held annually, until 2019 when it became one combined annual meeting of the ISTH and SSC. The conference covers clinical and basic aspects of hemostasis and thrombosis, and this year includes 5 Plenary lectures and >50 State of Art (SOA) lectures, presented by internationally recognized speakers, as well as numerous oral session and poster presentations selected from submitted abstracts, including many early career and reach the world support recipients. This SOA review article in RPTH contains concise Illustrated Review Articles or ‘Capsules’ consisting of short text, three references and a figure, with topics including stroke, cancer‐associated thrombosis, hemophilia, coagulation, the interface between infection and inflammation, and in the experimental and discovery areas, megakaryocyte biology and platelet production, structure‐function of key receptors and coagulation factors, and emerging new roles for thrombotic/hemostatic factors. Together, these articles highlight novel findings which will advance knowledge and with the potential to change clinical practice and improve outcomes. It is hoped that conference attendees and followers will enjoy utilizing the images for ongoing education and during the conference for live tweeting during sessions, to assist in the broadcasting and promotion of the science to those unable to attend, or who have chosen to attend a concurrent session. Use #IllustratedReview and #ISTH2019 on social media.

show abstract

Single cell coagulomes as constituents of the oncogene-driven coagulant phenotype in brain tumours

Cited by 23 publications

References 88 publications

Oncogenes and Clotting Factors: The Emerging Role of Tumor Cell Genome and Epigenome in Cancer-Associated Thrombosis

Oncogenes and Clotting Factors: The Emerging Role of Tumor Cell Genome and Epigenome in Cancer-Associated Thrombosis

Oncogenic Regulation of Extracellular Vesicle Proteome and Heterogeneity

Illustrated State‐of‐the‐Art Capsules of the ISTH 2019 Congress in Melbourne, Australia

Contact Info

Product

Resources

About