Background: Ovarian cancer (OC) is the most aggressive gynecologic cancer. Understanding OC molecular pathogenesis is critical to provide novel therapeutic strategies. We aim to elucidate Notch oncogenic role in OC by focusing on its extensive crosstalk with other important pathways as CXCR4/SDF1alpha chemokine system whose involvement in OC development and metastasis is well recognized. Methods: We used flow-cytometry, cell cycle analysis, real-time PCR, and Transwell chemotaxis assay to investigate the outcome of Notch signaling withdrawal on tumor cell response to CXCR4 and SDF1alpha. Results: The analyzed OC cell lines expressed high levels of CXCR4 and its ligand SDF1alpha. Treatment with DAPT, an inhibitor of Notch activity, reduced OC cell proliferation and blocked cell cycle in G0/G1 phase without affecting apoptosis. In addition, Notch withdrawal diminished CXCR4 and SDF1alpha expression levels and hampered SDF1-driven migration and proliferation. Conclusions: Notch deregulation might affect important features of OC such as cell growth and migration through the modulation of CXCR4/SDF1a pathway. This indicates that these intertwined pathways are promising therapeutic targets in OC.

Relationship of the oncogene Notch and CXCR4/SDF1 signaling in human epithelial ovarian cancer / V. Konala, N. Platonova, M. Colombo, L. Mirandola, E. Lazzari, D. De Simone, S. Radhi, A. Aulakh, K. Zepeda, R. Wade, J. Mer, C. Saadeh, Y. Yu, M. Jenkins, J.A. Figueroa, E. Cobos, M. Chiriva-Internati, R. Chiaramonte. - In: JOURNAL OF CLINICAL ONCOLOGY. - ISSN 1527-7755. - 31:15(2013 Jun 02), p. e7060. ((Intervento presentato al convegno ASCO Annual Meeting tenutosi a Chicago nel 2013.

Relationship of the oncogene Notch and CXCR4/SDF1 signaling in human epithelial ovarian cancer

N. Platonova
Secondo
;
M. Colombo;L. Mirandola;E. Lazzari;M. Chiriva-Internati
Penultimo
;
R. Chiaramonte
Ultimo
2013-06-02

Abstract

Background: Ovarian cancer (OC) is the most aggressive gynecologic cancer. Understanding OC molecular pathogenesis is critical to provide novel therapeutic strategies. We aim to elucidate Notch oncogenic role in OC by focusing on its extensive crosstalk with other important pathways as CXCR4/SDF1alpha chemokine system whose involvement in OC development and metastasis is well recognized. Methods: We used flow-cytometry, cell cycle analysis, real-time PCR, and Transwell chemotaxis assay to investigate the outcome of Notch signaling withdrawal on tumor cell response to CXCR4 and SDF1alpha. Results: The analyzed OC cell lines expressed high levels of CXCR4 and its ligand SDF1alpha. Treatment with DAPT, an inhibitor of Notch activity, reduced OC cell proliferation and blocked cell cycle in G0/G1 phase without affecting apoptosis. In addition, Notch withdrawal diminished CXCR4 and SDF1alpha expression levels and hampered SDF1-driven migration and proliferation. Conclusions: Notch deregulation might affect important features of OC such as cell growth and migration through the modulation of CXCR4/SDF1a pathway. This indicates that these intertwined pathways are promising therapeutic targets in OC.
Settore MED/04 - Patologia Generale
Settore MED/05 - Patologia Clinica
Settore MED/06 - Oncologia Medica
http://meetinglibrary.asco.org/content/113859-132
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/224705
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