12(S)-Hete-Induced Microvascular Endothelial Cell Retraction is Mediated by Cytoskeletal Rearrangement Dependent on PKC Activation

  • D. G. Tang
  • C. A. Diglio
  • K. V. Honn
Part of the Developments in Oncology book series (DION, volume 71)


Endothelial cells lining the vascular vessels used to be considered as a passive player in physiological hemostasis and many pathological processes. The past decade, however, has seen numerous challenges to this concept and now it is well appreciated that endothelial cells are actively involved in regulating a variety of biological processes including hemostasis and inflammation (1–3). In addition, experimental and clinical observations have pointed to the crucial role of endothelial cells in dissemination of blood-borne cancer cells (4–8). The importance of endothelial cells stems from the fact that they not only serve as a mechanical barrier to the passage of blood cells and components, they also possess versatile secreting functions and express various cell surface adhesion receptors that are directly involved in cell-cell interactions. Endothelial cells elaborate, among others, a variety of connective tissue components (e.g., collagen, fibronectin, thrombospondin and proteoglycans), proteolytic enzymes (e.g., elastase and collagenase), procoagulants (e.g., Factor V, tissue factor, etc), and growth factors and cytokines (e.g., PDGF and ECGF; IL-1, IL-8, etc) (1). Endothelial cells also carry out active arachidonic acid metabolism. The most prominent arachidonate metabolites of endothelial cells are prostacyclin (PGI2) derived from the cyclooxygenase pathway, and 13- hydrxyoctadecaenoic acid (13-HODE) derived from the lipoxygenase pathway. Additionally, endothelial cells also metabolize arachidonic acid to 12(S)-hydroxyeicosatetraenoic acid [12(S)- HETE] through the action of 12-lipoxygenase (15). It is well documented that prostacyclin derived from endothelial cells and thromboxane (TxA2) derived from platelets play an important regulatory role in maintaining the adhesivity of the vascular wall. Our recent experimental data suggest that another pair of eicosanoids, i.e., 12(S)-HETE from platelets and 13-HODE from endothelial cells, also modulate the adhesive state of the blood vessel wall (9, 10). Modulation of endothelial cell adhesiveness by various eicosanoids is achieved through cell surface adhesion molecules. The identification and characterization of a large number of adhesion molecules on endothelial cells represent one of the most important breakthroughs in the studies of the mechanism of endothelium-leukocyte and endothelium-tumor cell interactions. Moreover, endothelial cell adhesion molecules (Table 1) also play an essential role in maintaing the integrity of the monolayer.


Endothelial Cell Myosin Light Chain Kinase Endothelial Cell Dysfunction Endothelial Cell Monolayer Endothelial Cell Adhesion Molecule 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Springer Science+Business Media New York 1993

Authors and Affiliations

  • D. G. Tang
    • 1
  • C. A. Diglio
    • 3
  • K. V. Honn
    • 1
    • 2
    • 4
  1. 1.Department of Radiation OncologyWayne State UniversityUSA
  2. 2.Department of ChemistryWayne State UniversityUSA
  3. 3.Department of PathologyWayne State UniversityUSA
  4. 4.Gershenson Radiation Oncology CenterHarper HospitalDteroitUSA

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