Tissue factor expression provokes escape from tumor dormancy and leads to genomic alterations

Abstract

Significance Our study shows that the clotting protein tissue factor (TF) controls the state of tumor dormancy and does so in conjunction with recruitment of inflammatory cells and blood vessels. We show that indolent glioma cells remain harmless in mice unless rendered TF positive. Our work also demonstrates the ability of TF to indirectly influence the DNA of cancer cells by facilitating gene mutations and silencing. This ability is important because injury, cardiovascular disease, or other conditions may activate the clotting system and contribute to the awakening of occult cancer cells. This understanding also may suggest a prophylactic use of blood thinners in cases where dormant cancer cells and clotting are suspected to coexist (e.g., after surgery).

A preliminary estimation of tissue factor pathway inhibitor (TFPI) and protein C in patients with intracranial tumors

“…11 The histochemical and immunological tests of the tissue fragments derived from gliomas indicated a TF expression in tumor cells and in endothelium in new vessels created in the process of angiogenesis. 12 The present study confirms that the conversion of TF concentration per mg of protein in tumor tissue homogenate and, as compared to the plasma concentration of TF expressed per mg of protein in patients with intracranial tumors, makes us aware of the huge amount of TF present in intracranial tumor cells. It is well-known that normal brain cells contain particularly high TF, similar to lung and placenta cells.…”

“…Numerous studies show that TF plays an important role in the stimulation of cellular responses, gene transcription, cell survival and changes in cytoskeleton, i.e., the processes required for cell functioning in the microenvironment. 12,14 There are 2 known TF types: full-length TF or CD142, consisting of the extracellular, transmembrane and intracytoplasmatic parts (flTF) and, identified in 2003, alternatively spliced tissue factor (asTF). The flTF form is responsible for the activation of the coagulation process after damage to the endothelium by forming the complex with factor VII.…”

The contribution of tumor and host tissue factor expression to oncogene-driven gliomagenesis

“…U373vIII glioma cells were maintained with the addition of geneticin/G418 (5 lg/lL, GIBCO) and hygromycin (5 lg/lL, Invitrogen), as described earlier [10,16]. REMBRANDT: National Cancer Institute (2005), (http://rembrandt.nci.nih.gov) accessed July 10 2012.…”

The Dnmt1 Intrinsically Disordered Domain Regulates Genomic Methylation During Development

“…Primers for the EpiTYPER experiments are included in Table S2. DNA methylation standards (0, 33, 67, and 100%) were generated from mixtures of WT and Dnmt1 c/c ES-cell DNA.Genome-wide methylation was assessed using the reduced representation bisulfite sequencing (RRBS) technique (Boyle et al 2012) and analyzed according to the pipeline established at the McGill Epigenomics Mapping and Data Coordinating Centres in the McGill University and Génome Québec Innovation Centre (Magnus et al 2014). Sequencing was performed at the Tufts University Core Facility (TUCF Genomics) using an Illumina HiSequation 2500 rapid flow cell.…”