Abstract
Pseudomyxoma peritonei (PMP) is a peritoneal neoplastic disease arising from MUC2 producing goblet cells of the appendix and is characterized by the accumulation of massive amounts of mucinous ascites. Little is known about the tumor microenvironment that might give insight into the local inflammatory processes in the peritoneal cavity. The aim of this study was to characterize this tumor microenvironment in terms of cytokine expression, to determine their cellular source and biological effect on cell growth.|Multiplex cytokine assays were conducted on 37 ascites and 13 serum specimens from PMP patients to determine the cytokines expressed with a focus on pro-inflammatory cytokines. Tissue sections from 10 PMP specimens were immunostained for interleukin 6 (IL-6), interleukin 8 (IL-8), interferon inducible protein 10 (IP-10) and monocyte chemotactic protein 1 (MCP-1). Effects of IL-6 and IL-8 on cell growth were determined using recombinant human cytokines and the human mucinous colorectal cell line, LS174T (a surrogate for PMP cells).|The levels (median, range) of pg/ml of IL-6 (2493, 17.7-9267.97), IL-8 (208, 11.38-8847.03), IP-10 (3771, 72-11892) and MCP-1 (2856, 301-10726) in ascites were significantly elevated compared to serum levels of IL-6 (3.18, 1.41-32.08, p<0.0001), IL-8 (2.66, 1.52-96.94, p<0.0001), IP-10 (439.5, 213-884, p<0.0001) and MCP-1 (422, 143-3347, p=0.0002). Myoepithelial cells showed immunostaining for IL-6 and tumor cells stained faintly and moderately for IP-10 and MCP-1, respectively. Recombinant IL-6 and IL-8, at concentrations found in ascites, did not affect cell growth when measured over 72 hours.|In conclusion, this study has demonstrated high levels of IL-6, IL-8, IP-10 and MCP-1 in the tumor microenvironment of PMP. IL-6 and IL-8 do not affect growth of cells in vitro. Further studies are warranted to explore this dynamic environment in order to better classify this disease and to target treatment.