Leptin stimulates migration and invasion and maintains cancer stem-like properties in ovarian cancer cells: an explanation for poor outcomes in obese women.
Leptin stimulates migration and invasion and maintains cancer stem-like properties in ovarian cancer cells: an explanation for poor outcomes in obese women.
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DOI：
10.18632/oncotarget.4228
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发表时间：
2015-08-28
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影响因子：
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通讯作者：
Cuello MA
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文献类型：
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作者：
Kato S;Abarzua-Catalan L;Trigo C;Delpiano A;Sanhueza C;García K;Ibañez C;Hormazábal K;Diaz D;Brañes J;Castellón E;Bravo E;Owen G;Cuello MA
肥胖与卵巢癌之间的联系仍然存在争议。瘦素在肥胖女性中表达水平较高，并刺激其他上皮癌细胞的迁移。在这里，我们探讨了超重/肥胖对患者预后的临床影响和瘦素对卵巢癌细胞转移潜力的影响。我们评估了70例卵巢癌患者（33例健康体重和37例超重）的临床结局，这些患者通过癌症基因组图谱（TCGA）数据库的外部队列进行了验证。超重患者的无进展生存率和总生存率显著降低。同样，在表达较高瘦素/OB-Rb水平的TCGA患者中，总生存率较差。我们探讨了血清和腹水瘦素水平和OB-Rb的表达在我们的队列。血清和腹水瘦素水平较高的超重患者经历较差的生存。OB-Rb在腹水和转移瘤中的表达高于原发瘤。瘦素暴露通过瘦素介导的JAK/STAT 3、PI 3/AKT和RhoA/ROCK的活化增加癌细胞的迁移/侵袭，并促进新的板状伪足、应力纤维和粘着斑的形成。瘦素也有助于维持卵巢癌细胞的干细胞和间充质表型。我们的研究结果表明，瘦素刺激卵巢癌细胞的迁移和侵袭，为肥胖妇女的不良预后提供了一个潜在的解释。
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.