Abstract 2406: Metabolic phenotype and metastasis in patient-derived ovarian cancer xenografts
Authors: MariaRosa Bani, Carmen Ghilardi, Alessandra Decio, Alessia Anastasia, Martina Verza, Stefano Indraccolo, Raffaella Giavazzi
Journal: Cancer Research (2018)

Abstract Introduction and Aim Metabolic re-programming is an emerging hallmark of cancer. Alterations of the metabolism of glucose (i.e. glycolysis) and oxidative phoshorylation (OxPhos) are frequently observed in cancer cells. Ovarian adenocarcinoma (OC) is the third most common gynecologic malignancy in the developed countries and the most lethal one, which has shown little improvement in overall survival for the last 20 years. OC is a widely metastatic disease disseminating to the organs of the abdomen through ascitic effusion. Understanding the mechanisms facilitating metastatic spread and disease recurrence is needed to develop therapeutic strategies.Our aim is the comprehension of the metabolic perturbations favoring the aggressiveness and metastatic dissemination of OC. Experimental methods We characterized a panel of OC-patient derived xenografts (OC-PDX) for their malignant behavior (ascites production, abdominal metastasis formation and survival time). Their metabolic features were depicted as i) glucose and lactate levels measured in ascites, ii) the monocarboxyate transporters MCT1 and MCT4 of the abdominal tumor masses (by IHC), iii) glycolysis- and OxPhos- related enzymes, as well as glucose and lactate transporters (by gene expression) in abdominal masses and ascites. Results We found a direct correlation between the amount of lactate and the expression of its transporters, thus OC-PDX showing higher expression of MC1/MCT4 and higher amount of lactate were categorized as “high glycolytic” and those with lower MCT1/MCT4 and lactate “low glycolytic”. The low glycolytic OC-PDXs developed more abdominal metastasis than the highly glycolytic ones, indicating an inverse correlation between the glycolytic phenotype and the capability of the OC-PDX to disseminate, invade and grow into the organs of the peritoneal cavity. Interestingly, we found that the abdominal masses express lower levels of the glucose transporters (i.e. GLUT1), glycolysis-related enzymes (i.e. HK, LDHA) and MCT4 compared to cell aggregates from abdominal effusion; suggesting that ovarian cancer cells are able to modulates their metabolism (glycolysis/OxPhos) to best fit the needs favoring metastatic spread. Further studies are needed to fully understand this association. Conclusions Nowadays, metabolism is potentially "targetable”. Our results strongly indicate that perturbing tumor's metabolic re-programming might affect metastatic dissemination. M R B and C G contributed equally. Supported by Italian Association for Cancer Research (AIRC) IG2016 18853 to RG. Citation Format: MariaRosa Bani, Carmen Ghilardi, Alessandra Decio, Alessia Anastasia, Martina Verza, Stefano Indraccolo, Raffaella Giavazzi. Metabolic phenotype and metastasis in patient-derived ovarian cancer xenografts [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2406.