PAN02 PANCREATIC TUMOR MODELS CARRYING THE GFP MARKER IN MICE

Abstract

Animal tumor models are used for preclinical studies of drugs and cancer therapy. The aim of this work was to analyze the growth of murine pancreatic tumor cells Pan02, carrying GFP marker, injected subcutaneously (s.c.), intraperitoneally (i.p.) or orthotopically into the pancreas (ortho) of C57BL/6 mice. Mice were injected with 2´10⁵ cells: s.c. in the right flank; i.p. with a syringe into the abdominal cavity, or ortho surgically under the pancreas capsule. The weight of mice was determined in the dynamics of tumor growth, and blood serum was taken to analyze the antibody response to the GFP reference protein. At the 2nd and 4th weeks of tumor growth, some mice were slaughtered and the expression of GFP by the tumor cells, as well as the composition of the immune cells in the tumor, were analyzed by flow cytometry and confocal microscopy. It was shown that with the different localization, the pancreatic tumors grew at different rates and lethality. When the tumor was injected i.p., mice lost weight with rapid tumor growth. In the ortho model, the mice increased their weight. Mortality in the s.c. and i.p. groups was comparable. In the s.c. model, the tumor grew slowly to a volume of 200-400 mm3 and stopped growing. There was no mortality in this group during the follow-up period (2 months). The same antibody response to GFP was formed with all injection schemes. The subpopulation composition of immune cells varied greatly in the different models of tumor cell administration. Regardless of the type of immune response, Pan02-GFP cells rapidly suppressed GFP gene expression in vivo. The data obtained showed that murine pancreatic tumor Pan02 is immunogenic and causes the formation of an adaptive immune response. Regardless of the presence or absence of an immune response and elimination of GFP+ cells, the tumor continued to grow in the i.p. and ortho models, but not in the s.c. one, and caused the death of mice. When conducting preclinical studies, it is necessary to use several ways of tumor cell injection to obtain a more objective result.