Oncotarget

Research Papers:

Leptin stimulates migration and invasion and maintains cancer stem-like properties in ovarian cancer cells: an explanation for poor outcomes in obese women

Sumie Kato, Lorena Abarzua-Catalan, César Trigo, Ana Delpiano, Cristobal Sanhueza, Karen García, Carolina Ibañez, Katherine Hormazábal, Daniela Diaz, Jorge Brañes, Enrique Castellón, Erasmo Bravo, Gareth Owen and Mauricio A. Cuello _

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Oncotarget. 2015; 6:21100-21119. https://doi.org/10.18632/oncotarget.4228

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Abstract

Sumie Kato1, Lorena Abarzua-Catalan1, César Trigo1, Ana Delpiano1, Cristobal Sanhueza2, Karen García1, Carolina Ibañez2, Katherine Hormazábal1, Daniela Diaz1, Jorge Brañes1, Enrique Castellón4, Erasmo Bravo5, Gareth Owen3 and Mauricio A. Cuello1

1 Division of Obstetrics and Gynecology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile

2 Department Hematology and Oncology, Pontificia Universidad Católica de Chile, Santiago, Chile

3 Department of Physiological Sciences, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile

4 Faculty of Medicine, University of Chile, Santiago, Chile

5 Gynecologic Oncology Unit, Hospital Gustavo Fricke, Viña del Mar, Chile

Correspondence to:

Mauricio A. Cuello, email:

Keywords: leptin, ovary, neoplasia, metastasis, obesity

Received: March 10, 2015 Accepted: May 13, 2015 Published: May 22, 2015

Abstract

The evidence linking obesity with ovarian cancer remains controversial. Leptin is expressed at higher levels in obese women and stimulates cell migration in other epithelial cancers. Here, we explored the clinical impact of overweight/obesity on patient prognosis and leptin’s effects on the metastatic potential of ovarian cancer cells. We assessed clinical outcomes in 70 ovarian cancer patients (33 healthy weight and 37 overweight) that were validated with an external cohort from The Cancer Genome Atlas (TCGA) database. Progression-free and overall survival rates were significantly decreased in overweight patients. Similarly, a worse overall survival rate was found in TCGA patients expressing higher leptin/OB-Rb levels. We explored serum and ascites leptin levels and OB-Rb expression in our cohort. Serum and ascites leptin levels were higher in overweight patients experiencing worse survival. OB-Rb was more highly expressed in ascites and metastases than in primary tumors. Leptin exposure increased cancer cell migration/invasion through leptin-mediated activation of JAK/STAT3, PI3/AKT and RhoA/ROCK and promoted new lamellipodial, stress-fiber and focal adhesion formation. Leptin also contributed to the maintenance of stemness and the mesenchymal phenotype in ovarian cancer cells. Our findings demonstrate that leptin stimulated ovarian cancer cell migration and invasion, offering a potential explanation for the poor prognosis among obese women.


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