Die PGK1 Überexpression im Magenkarzinom induziert Metastasierung und peritoneale Tumoraussaat Induction of metastases and peritoneal carcinomatosis in gastric cancer by overexpression of PGK1

Introduction: Peritoneal carcinomatosis and metastases is a frequent finding in diffuse gastric cancer patients and is associated with a poor prognosis. The enhanced expression of phosphoglycerate kinase 1 (PGK1) seems to play a crucial role in enabling diffuse primary gastric tumours to develop peritoneal dissemination. Material and Methods: A metastatic mouse model was established simulating human gastric cancer behaviour by orthotopic implantation of histologically intact tumor tissue with (n = 7) and without (n = 7) overexpression of PGK1 onto the serosa of nude mice. PET-MRTimaging was performed to evaluate peritoneal carcinomatosis and metastases in-vivo. Subsequent the animals were examined for tumor growth and metastases by histopathological evaluation and compared among each other. Results: Histopathological examinations revealed that overexpression of PGK1 significantly increased peritoneal carcinomatosis and metastases of human gastric cancer in nude mice. The mean tumorindex (tumorweight in relation to the body weight of the animals in %) in PGK1 overexpressed mice was 15.9 % and in the non-overexpressed mice by 8.4 % (p = 0.006). We were further able to confirm this findings in-vivo using PET-MRT-imaging, showing a strong correlation to the obtained histopathological alterations. Conclusion: The overexpression of PGK1 appears to be a crucial enzyme enabling gastric tumor cells to disseminate. Thus, PGK1 may serve in future as prognostic marker and/or be a potential therapeutic target to prevent peritoneal carcinomatosis and metastases in gastric cancer. Einleitung