A new peritoneal dissemination model established from human pancreatic cancer cell line

We established a new cell line, HPC-3P4a, with high peritoneal disseminated potential in nude mice. HPC-3P4a was derived from a human pancreatic carci noma cell line (HPC-3) that had low capacity for peritoneal dissemination H PC-3P4a developed peritoneal dissemination in 10 of 11 (90.9%) cases, where as parental HPC-3 developed peritoneal dissemination in one of six (16.7%) cases. The metastatic foci in the peritoneum showed essentially the same hi stologic appearance of parental involvement. The tumorigenicity, motility, and adhesive activity of HPC-3P4a to the extracellular matrix were stronger than were those of the HPC-3. In FAGS analysis, HPC-3P4a significantly inc reased the expression of alpha6 and alphav beta5 integrins, while it decrea sed alpha2 integrin, hCD44H, and hCD44v10, as compared with HPC-3. The VEGF production of HPC-3P4a was significantly tower than that of HPC-3. Analysi s of gene macroarrays showed a variety of cytokines, interleukin, and other immunomodulatory, and their receptors were up-regulated and down-regulated on an mRNA level in HPC-3P4a cells, compared with HPC-3 cells. Intraspleni c injection of HPC-3P4a produced no liver metastasis. We named our original highly liver metastatic cell line HPC-3H4 (previously reported). This HPC- 3H4 cell was established by repeated intrasplenic injection from parental c ell HPC-3; thus, it developed high liver metastasis. Moreover, HPC-3H4 deve loped peritoneal dissemination by intra-abdominal injection. In contrast, H PC-3P4a did not develop liver metastasis by intrasplenic injection. These f indings are very interesting and might suggest that the process of hematoge nous metastasis differed from that of peritoneal dissemination. Thus, this cell line may be useful for investigating the mechanism of peritoneal disse mination in human pancreatic cancer.