Related Experiment Video
Updated: Mar 21, 2026
03:53
Author Spotlight: High-Sensitivity Tissue Factor Activity Assay for Plasma Diagnosis
Published on: December 29, 2023
1.3K
PO-44 - Tissue factor pathway inhibitor-2 (TFPI-2) is cleaved by PRSS3: implication for tumor endothelial cells
C Ghilardi1, A Anastasia1, R Avigni1
1IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Dept. of Oncology, Milan, Italy.
Thrombosis Research
|May 11, 2016
Summary
Tissue Factor Pathway Inhibitor-2 (TFPI-2) inhibits endothelial cell migration, but PRSS3 degrades TFPI-2, promoting tumor angiogenesis. Silencing PRSS3 increases TFPI-2, inhibiting tumor-associated endothelial cell migration.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Tissue Factor Pathway Inhibitor-2 (TFPI-2) is a Kunitz-type serine proteinase inhibitor.
- TFPI-2 expression is upregulated by VEGF in endothelial cells (EC).
- TFPI-2 is considered anti-angiogenic, inhibiting EC migration and proliferation.
Purpose of the Study:
- Investigate TFPI-2's role in tumor vasculature.
- Elucidate the mechanism of TFPI-2 function regulation in tumor endothelium.
- Determine the impact of TFPI-2 on angiogenesis and vascular remodeling in cancer progression.
Main Methods:
- Isolated tumor-EC from ovarian carcinomas and cultured in vitro.
- Utilized small interfering RNA (siRNA) for TFPI-2 and PRSS3 silencing.
- Assayed tumor-EC migration using wound healing assay; analyzed transcript expression via qRT-PCR and protein degradation via western blot.
Main Results:
- Tumor-EC express TFPI-2, primarily localized in the extracellular matrix.
- TFPI-2 silencing enhanced tumor-EC migration, confirming its anti-angiogenic role.
- PRSS3 directly degrades TFPI-2 in cell-free systems and removes it from the extracellular matrix.
- PRSS3 silencing led to TFPI-2 accumulation and inhibited tumor-EC migration.
Conclusions:
- TFPI-2 is a direct substrate of PRSS3, which inactivates its anti-migratory function.
- PRSS3-mediated proteolytic inactivation of TFPI-2 promotes tumor angiogenesis and vascular remodeling.
- This mechanism may contribute to cancer progression by enhancing tumor vascularization.
Related Concept Videos
01:20Extrinsic and Intrinsic Pathways of Hemostasis
15.1K
Blood clotting or coagulation involves extrinsic and intrinsic pathways, which ultimately merge into the common pathway, forming a fibrin clot.
The Extrinsic Pathway
The extrinsic pathway of coagulation is typically initiated by tissue damage that exposes blood to tissue factor (TF), a protein released by the damaged tissue cells outside the blood vessels—this interaction with TF triggers biochemical reactions involving specific clotting factors. The key player here is Factor VII, which...
The Extrinsic Pathway
The extrinsic pathway of coagulation is typically initiated by tissue damage that exposes blood to tissue factor (TF), a protein released by the damaged tissue cells outside the blood vessels—this interaction with TF triggers biochemical reactions involving specific clotting factors. The key player here is Factor VII, which...
15.1K
01:16Clot Retraction and Fibrinolysis
10.0K
After a fibrin clot is formed, the next step is clot retraction, a vital process facilitated by platelet contractile proteins, such as actin and myosin. These proteins pull the fibrin strands closer together and condense the clot. This action reduces the size of the clot, creating a smaller, denser structure that effectively seals off the damaged vessel. Clot retraction consolidates the clot and helps with wound healing by bringing the edges of the damaged blood vessel closer together.
10.0K
01:17Intracellular Signaling Affects Focal Adhesions
3.8K
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
3.8K
01:22Formation of the Platelet Plug
10.5K
The platelet phase, the second stage of hemostasis, commences around 15-20 seconds after an injury. It follows and overlaps with the vascular phase, during which blood vessels constrict to minimize blood loss.
As the injured blood vessel contracts, endothelial cells undergo contraction, revealing collagen fibers in the basement membrane and underlying connective tissue. Furthermore, the plasma membrane of endothelial cells becomes adhesive, preparing the site for platelet adhesion. Platelets...
As the injured blood vessel contracts, endothelial cells undergo contraction, revealing collagen fibers in the basement membrane and underlying connective tissue. Furthermore, the plasma membrane of endothelial cells becomes adhesive, preparing the site for platelet adhesion. Platelets...
10.5K
01:20The JAK-STAT Signaling Pathway
13.7K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
13.7K