Reduced basal and stimulated leukocyte adherence in tumor endothelium of experimental pancreatic cancer

Int J Pancreatol. 1999 Dec;26(3):173-9. doi: 10.1385/IJGC:26:3:173.

Abstract

Background: The interaction between immunocompetent cells and tumor endothelium is essential for an effective immunological response. In the present study, we evaluated resting and CD11b/CD18-mediated leukocyte adhesion in tumor vessels of experimental pancreatic cancer and in healthy pancreatic venules in the rat.

Methods: Solid tumor fragments (1 mm3) were interposed intrapancreatically between inert transparent polymethylmetacrylate plates for intravital microscopy (n = 12) by which tumor microcirculation, leukocyte-tumor-endothelium interaction, and the effect of the chemoattractants N-formyl-methioninleucylphenylalanine (fMLP) and platelet-activating factor (PAF) on leukocyte adherence was investigated.

Results: Leukocyte adhesion in pancreatic tumor vessels was significantly reduced compared to healthy pancreatic venules. Both fMLP and PAF dramatically increased leukocyte adherence in normal pancreatic venules. No change in leukocyte adhesion was present in tumor vessels after exposure to these chemotactic substances.

Conclusion: Resting and stimulated integrin-dependent leukocyte adhesion is strongly reduced in malignant vessels of experimental pancreatic cancer, which may be an important mechanism to escape immune control.

MeSH terms

  • Animals
  • Blood Flow Velocity
  • Blood Vessels / metabolism
  • Carcinoma / blood supply
  • Carcinoma / pathology*
  • Carcinoma / physiopathology*
  • Cell Adhesion / drug effects
  • Cell Adhesion / physiology
  • Chemotactic Factors / pharmacology
  • Endothelium / physiopathology*
  • Endothelium, Vascular / physiopathology
  • Erythrocytes / physiology
  • Leukocytes / physiology*
  • Lymphocyte Culture Test, Mixed
  • N-Formylmethionine Leucyl-Phenylalanine / metabolism
  • Pancreatic Neoplasms / blood supply
  • Pancreatic Neoplasms / pathology*
  • Pancreatic Neoplasms / physiopathology*
  • Platelet Activating Factor / metabolism
  • Rats
  • Venules

Substances

  • Chemotactic Factors
  • Platelet Activating Factor
  • N-Formylmethionine Leucyl-Phenylalanine