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Diabetic concentrations of metformin inhibit platelet-mediated ovarian cancer cell progression.
Erices, Rafaela; Cubillos, Sofía; Aravena, Raúl; Santoro, Felice; Marquez, Monica; Orellana, Renan; Ramírez, Carolina; González, Pamela; Fuenzalida, Patricia; Bravo, María Loreto; Oliva, Bárbara; Kato, Sumie; Ibañez, Carolina; Brañes, Jorge; Bravo, Erasmo; Alonso, Catalina; García, Karen; Arab, Clemente; Torres, Vicente A; Godoy, Alejandro S; Pereira, Jaime; Bustos, Galdo; Cardenas, Julio Cesar; Cuello, Mauricio A; Owen, Gareth I.
Afiliação
  • Erices R; Division of Obstetrics and Gynecology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
  • Cubillos S; Department of Physiological Sciences, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile.
  • Aravena R; Department of Physiological Sciences, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile.
  • Santoro F; Department of Physiological Sciences, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile.
  • Marquez M; Universidad Santo Tomás, Santiago, Chile.
  • Orellana R; Department of Physiological Sciences, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile.
  • Ramírez C; Department of Physiological Sciences, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile.
  • González P; Division of Obstetrics and Gynecology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
  • Fuenzalida P; Universidad Bernardo OHiggins, Facultad de Salud, Departamento de Ciencias Químicas y Biológicas, General Gana, Santiago, Chile.
  • Bravo ML; Department of Physiological Sciences, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile.
  • Oliva B; Department of Physiological Sciences, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile.
  • Kato S; Biomedical Research Consortium of Chile, Santiago, Chile.
  • Ibañez C; Department of Physiological Sciences, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile.
  • Brañes J; Department of Physiological Sciences, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile.
  • Bravo E; Biomedical Research Consortium of Chile, Santiago, Chile.
  • Alonso C; Millennium Institute on Immunology and Immunotherapy, Pontificia Universidad Católica de Chile, Santiago, Chile.
  • García K; Department of Physiological Sciences, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile.
  • Arab C; Biomedical Research Consortium of Chile, Santiago, Chile.
  • Torres VA; Division of Obstetrics and Gynecology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
  • Godoy AS; Millennium Institute on Immunology and Immunotherapy, Pontificia Universidad Católica de Chile, Santiago, Chile.
  • Pereira J; Hematology and Oncology Department, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
  • Bustos G; Center UC Investigation in Oncology, Pontificia Universidad Católica de Chile, Santiago, Chile.
  • Cardenas JC; Division of Obstetrics and Gynecology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
  • Cuello MA; Hospital Gustavo Fricke, Viña de Mar, Santiago, Chile.
  • Owen GI; Hospital Gustavo Fricke, Viña de Mar, Santiago, Chile.
Oncotarget ; 8(13): 20865-20880, 2017 Mar 28.
Article em En | MEDLINE | ID: mdl-28209916
Clinical studies have suggested a survival benefit in ovarian cancer patients with type 2 diabetes mellitus taking metformin, however the mechanism by which diabetic concentrations of metformin could deliver this effect is still poorly understood. Platelets not only represent an important reservoir of growth factors and angiogenic regulators, they are also known to participate in the tumor microenvironment implicated in tumor growth and dissemination. Herein, we investigated if diabetic concentrations of metformin could impinge upon the previously reported observation that platelet induces an increase in the tube forming capacity of endothelial cells (angiogenesis) and upon ovarian cancer cell aggressiveness. We demonstrate that metformin inhibits the increase in angiogenesis brought about by platelets in a mechanism that did not alter endothelial cell migration. In ovarian cancer cell lines and primary cultured cancer cells isolated from the ascitic fluid of ovarian cancer patients, we assessed the effect of combinations of platelets and metformin upon angiogenesis, migration, invasion and cancer sphere formation. The enhancement of each of these parameters by platelets was abrogated by the present of metformin in the vast majority of cancer cell cultures tested. Neither metformin nor platelets altered proliferation; however, metformin inhibited the increase in phosphorylation of focal adhesion kinase induced by platelets. We present the first evidence suggesting that concentrations of metformin present in diabetic patients may reduce the actions of platelets upon both endothelial cells and cancer cell survival and dissemination.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Plaquetas / Diabetes Mellitus Tipo 2 / Hipoglicemiantes / Metformina / Neovascularização Patológica Limite: Female / Humans Idioma: En Revista: Oncotarget Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Chile

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Plaquetas / Diabetes Mellitus Tipo 2 / Hipoglicemiantes / Metformina / Neovascularização Patológica Limite: Female / Humans Idioma: En Revista: Oncotarget Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Chile