Influence of Gastrointestinal Hormones on Tumor Microcirculation of Experimental Pancreatic Cancer in the Rat

Abstract

Background/Aims: Gastrointestinal hormones influence the microcirculation in the normal pancreas. In the present study, we studied the effect of cerulein and somatostatin on pancreatic cancer microcirculation after orthotopic and nonorthotopic tumor implantation. Methods: In 36 male Lewis rats (150–180 g) induction of a ductlike pancreatic cancer was achieved by intrapancreatic or intraperitoneal tumor fragment interposition between two inert transparent polymethyl methacrylate plates. After 4 weeks, intravital microscopy of the tumor microcirculation was performed in a temperature-controlled immersion chamber. The animals received 5 μg/kg cerulein or 3 mg/kg somatostatin for 1 h intravenously. The erythrocyte velocity in normal pancreatic capillaries or in tumor vessels was measured. Results: The erythrocyte velocity in the capillaries of the normal pancreas was 1.01 ± 0.11 mm/s at baseline and increased to 1.64 ± 0.09 mm/s after cerulein stimulation (p = 0.007). Pancreatic cancer vessels demonstrated no increase in erythrocyte velocity after orthotopic (baseline 0.95 ± 0.14 mm/s, after 1 h 0.86 ± 0.13 mm/s; n.s.) and nonorthotopic tumor implantation (baseline 0.91 ± 0.12 mm/s, after 1 h 0.95 ± 0.14 mm/s; n.s.) after cerulein stimulation. Somatostatin decreased the erythrocyte velocity both in normal pancreas (baseline 0.87 ± 0.02 mm/s, after 1 h 0.60 ± 0.07 mm/s; p = 0.01) and in pancreatic cancer (baseline 0.85 ± 0.20 mm/s, after 1 h 0.63 ± 0.18 mm/s; p = 0.02) after orthotopic tumor implantation. There was no effect of somatostatin after nonorthotopic tumor implantation (baseline 0.90 ± 0.10 mm/s, after 1 h 0.88 ± 0.14 mm/s; n.s.). Conclusion: These data suggest that pancreatic cancer microcirculation lacks physiological blood flow control by stimulatory hormones, in contrast to the normal pancreas.