Cellular Interactions and NK Cell-Activation in Early Liver Metastasis.

Project Details

Description

Pit cells induce cytolyis and apoptosis in syngenic CC531s colon carcinoma cells in vitro. This cytotoxicity is enhanced when pit cells cooperate with Kupffer cells. When one million CC531s cells are injected into a mesenteric vein, only a few dozen metastatic nodules develop. Our working hypothesis is, that this substantial metastatic-inefficiency is based on the defensive action of pit cells and Kupffer cells. Almost all studies in this field are based on in vitro studies, and therefore almost nothing is know about the events in vivo. In this project we want to investigate: i) what cellular interactions are taking place soon after arrival of a tumor cell in a hepatic sinusoid, ii) how 99% of the tumor cells disappear, and iii) how tumor cells escape from the defense system and extravasate. Due to the low frequency of the phenomena, we have to use the confocal laser scanning microscope. This microscope is able to detect fluorescent cells in a large volume of tissue and is able to visualize cells in great detail. By using three detection channels, we will be able to use an equal number of probes or stains simultaneously. We hope to have GFP-fluorescent CC531 cells soon. By using different probes we will be able to distinguish (activated) pit cells (mAB 3.2.3, ANK66) or Kupffer cells (ED2, latex) from endothelial cells (DiI-LDL). Aim of the study is to acquire knowledge on the exact cellular mechanisms of defense against metastasis in the liver, and to propose methods for the enhancement of the hepatic cellular defense to further suppress metastasis.
AcronymFWOAL127
StatusFinished
Effective start/end date1/01/9931/12/03

Keywords

  • Cellular Immune Defense System
  • Liver
  • Cellular Interactions
  • Colon Carcinoma Cells
  • Confocal Laser

Flemish discipline codes

  • Basic sciences