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Genetic Perturbation of Pyruvate Dehydrogenase Kinase 1 Modulates Growth, Angiogenesis and Metabolic Pathways in Ovarian Cancer Xenografts.
Venturoli, Carolina; Piga, Ilaria; Curtarello, Matteo; Verza, Martina; Esposito, Giovanni; Venuto, Santina; Navaglia, Filippo; Grassi, Angela; Indraccolo, Stefano.
Afiliación
  • Venturoli C; Immunology and Molecular Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, 35128 Padova, Italy.
  • Piga I; Immunology and Molecular Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, 35128 Padova, Italy.
  • Curtarello M; Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy.
  • Verza M; Immunology and Molecular Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, 35128 Padova, Italy.
  • Esposito G; Immunology and Molecular Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, 35128 Padova, Italy.
  • Venuto S; Immunology and Molecular Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, 35128 Padova, Italy.
  • Navaglia F; Department of Biology, University of Padova, 35128 Padova, Italy.
  • Grassi A; Department of Laboratory Medicine, University Hospital of Padova, 35128 Padua, Italy.
  • Indraccolo S; Immunology and Molecular Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, 35128 Padova, Italy.
Cells ; 10(2)2021 02 05.
Article en En | MEDLINE | ID: mdl-33562444
Pyruvate dehydrogenase kinase 1 (PDK1) blockade triggers are well characterized in vitro metabolic alterations in cancer cells, including reduced glycolysis and increased glucose oxidation. Here, by gene expression profiling and digital pathology-mediated quantification of in situ markers in tumors, we investigated effects of PDK1 silencing on growth, angiogenesis and metabolic features of tumor xenografts formed by highly glycolytic OC316 and OVCAR3 ovarian cancer cells. Notably, at variance with the moderate antiproliferative effects observed in vitro, we found a dramatic negative impact of PDK1 silencing on tumor growth. These findings were associated with reduced angiogenesis and increased necrosis in the OC316 and OVCAR3 tumor models, respectively. Analysis of viable tumor areas uncovered increased proliferation as well as increased apoptosis in PDK1-silenced OVCAR3 tumors. Moreover, RNA profiling disclosed increased glucose catabolic pathways-comprising both oxidative phosphorylation and glycolysis-in PDK1-silenced OVCAR3 tumors, in line with the high mitotic activity detected in the viable rim of these tumors. Altogether, our findings add new evidence in support of a link between tumor metabolism and angiogenesis and remark on the importance of investigating net effects of modulations of metabolic pathways in the context of the tumor microenvironment.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Ováricas / Piruvato Deshidrogenasa Quinasa Acetil-Transferidora Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans Idioma: En Revista: Cells Año: 2021 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Suiza
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Ováricas / Piruvato Deshidrogenasa Quinasa Acetil-Transferidora Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans Idioma: En Revista: Cells Año: 2021 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Suiza