Tissue factor controls the balance of angiogenic and antiangiogenic properties of tumor cells in mice.
Youming Zhang,Youhua Deng,Thomas Luther,Martin Müller,Reinhard Ziegler,Rüdiger Waldherr,David M. Stern,Peter P. Nawroth +7 more
TLDR
The results suggest that tissue factor regulates angiogenic properties of tumor cells by altering the production of growth regulatory molecules of endothelium by a mechanism distinct from tissue factor activation of the coagulation mechanism.Abstract:
Meth-A sarcoma cells were stable transfected to overexpress (sense construct) or underexpress (antisense construct) tissue factor. In vitro, there was no difference in plating efficiency or growth between these cell lines. In vivo, tumor cells transfected to overexpress tissue factor grew more rapidly, and established larger and more vascularized tumors than control transfectants. Antisense transfectants grew the slowest and were the least vascularized. Anticoagulation of mice with warfarin did not alter the difference between these tumor lines. Tumor cells over-expressing tissue factor released more (compared with control transfectants) mitogenic activity for endothelial cells in parallel with enhanced transcription of vascular permeability factor/vascular endothelial cell growth factor (VEGF/VPF), and diminished transcription of thrombospondin (TSP2), a molecule with anti-angiogenic properties. Antisense tissue factor transfectants, while releasing the lowest amount of mitogenic activity, had increased thrombospondin and decreased VEGF/VPF transcription compared with control transfectants or wild-type cells. Experiments with these sense, antisense, truncated sense, or vector tumor lines gave comparable results in complete medium, serum free medium or in the presence of hirudin, indicating that the activation of the coagulation mechanism was not likely to be responsible for changes in tumor cell properties. These results suggest that tissue factor regulates angiogenic properties of tumor cells by altering the production of growth regulatory molecules of endothelium by a mechanism distinct from tissue factor activation of the coagulation mechanism.read more
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Endothelial Cells in Physiology and in the Pathophysiology of Vascular Disorders
Douglas B. Cines,Eleanor S. Pollak,Clayton A. Buck,Joseph Loscalzo,Guy A. Zimmerman,Rodger P. McEver,Jordan S. Pober,Timothy M. Wick,Barbara A. Konkle,Bradford S. Schwartz,Elliot S. Barnathan,Keith R. McCrae,Bruce A. Hug,Ann Marie Schmidt,David M. Stern +14 more
TL;DR: The membrane has long been viewed as an inert cellophane-like membrane that lines the circulatory system with its primary essential function being the maintenance of vessel wall permeability.
Journal ArticleDOI
The role of tumour‐associated macrophages in tumour progression: implications for new anticancer therapies
TL;DR: Evidence for the number and/or distribution of TAMs being linked to prognosis in different types of human malignancy is presented and the range of pro‐ and anti‐tumour functions performed by TAMs are outlined, and the novel therapies recently devised using TAMs to stimulate host immune responses or deliver therapeutic gene constructs to solid tumours are outlined.
Journal ArticleDOI
The vascular endothelial growth factor receptor Flt-1 mediates biological activities. Implications for a functional role of placenta growth factor in monocyte activation and chemotaxis.
Matthias Clauss,Herbert A. Weich,Georg Breier,Ulrike E. Knies,Wolfgang Röckl,Johannes Waltenberger,Werner Risau +6 more
TL;DR: Findings strongly suggest Flt-1 as a functional receptor for VEGF and PlGF in monocytes and endothelial cells and identify this receptor as a mediator of monocyte recruitment and procoagulant activity.
Journal ArticleDOI
Abnormal angiogenesis and responses to glucose and oxygen deprivation in mice lacking the protein ARNT
Emin Maltepe,Jennifer V. Schmidt,David A. Baunoch,Christopher A. Bradfield,M. Celeste Simon,M. Celeste Simon +5 more
TL;DR: A model in which increasing tissue mass during organogenesis leads to the formation of hypoxic/nutrient-deprived cells, the subsequent activation of ARNT, and a concomitant increase in the expression of genes that promote vascularization of the developing yolk sac and solid tissues is proposed.
Journal ArticleDOI
Role of tissue factor in embryonic blood vessel development
Peter Carmeliet,Nigel Mackman,Lieve Moons,Thomas Luther,Pierre Gressens,I Van Vlaenderen,H Demunck,Michael Kasper,Georg Breier,Philippe Evrard,Martin Müller,Werner Risau,Thomas S. Edgington,Desire Collen +13 more
TL;DR: It is reported that inactivation of the tissue factor gene (TF) results in abnormal circulation from yolk sac to embryo beyond embryonic day 8.5, leading to embryo wasting and death, implying that tissue factor has a role in bloodvessel development.
References
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