**Hemostatic System in Malignancy: Providing the "Soil" in Metastatic Niche Formation**

Elina Beleva, Veselin Popov and Janet Grudeva-Popova

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/64697

#### **Abstract**

Malignancy arises and progresses in tight association with changes in the tumor microenvironment and deregulation of hemostatic system. Cancer induces hemostatic imbalance through production and secretion of procoagulant substances, suppression of anticoagulant mechanisms, endothelial activation, and angiogenic switch. Cancer cells are equipped with certain coagulation signaling receptors such as tissue factor (TF) and urokinase plasminogen activator receptor (uPAR). Tissue factor: as major initiator of coagulation, TF is considered the main cause for hypercoagulability in cancer. Constitutive TF expression by cancer cells is a hallmark of malignancy rendering tumors proangiogenic and prometastatic. TF fosters metastasis through coagulation-depend‐ ent pathways leading to fibrin deposition in the evolving premetastatic niche. TF has been identified as an independent predictor for metastatic development and adverse prognosis. uPAR: Tissue overexpression of uPAR is demonstrated in almost all human cancers and is associated with advanced disease. Increased uPAR expression is driven by molecular events involving K-ras and SRC oncogenes. Transactivation of these receptors, mediated by binding to hemostatic proteins, activates intracellular signal‐ ing pathways, modulates gene expression and facilitates processes of tumor initiation, epithelial-to-mesenchymal transition, anoikis, and metastasis. By manipulating hemostatic processes, tumor induces tolerant host environment necessary for evasion of defense attacks, survival, and progression.

**Keywords:** hemostasis, cancer, metastasis, tissue factor, urokinase plasminogen acti‐ vator

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
