title: Targeting Leptin as a Therapeutic Strategy against Ovarian Cancer Peritoneal Metastasis.
abstract: OBJECTIVE
  Epithelial ovarian cancer (OC) is the leading cause of death in patients with gynecologic malignancy. Malignant ascites, a shared symptom of advanced OC patients, plays an important role in the peritoneal metastasis cascade of OC. Since leptin existed in great amount in malignant ascites, we speculated that it might be involved in the modulation of tumor cells malignant behavior.
  
  
  METHODS
  Here, we demonstrated that blocking of leptin could significantly suppress ovarian malignant ascitesinduced metastatic aggravation of OC cells. Furthermore, our results suggested that leptin was highly expressed in OC and correlated with poor outcome of OC patients. Recombinant leptin notably promoted the migration, invasion and proliferation of OC cells.
  
  
  RESULTS
  Mechanistically, we found that leptin induced epithelial-mesenchymal transition (EMT) program in OC cells through the activation of the PI3K/Akt/mTOR pathway. Pharmacological inhibition of the PI3K/Akt/mTOR pathway partly impaired leptin-induced malignant transformation of OC cells. More importantly, our in vivo xenograft experiment showed that blocking of leptin could dramatically inhibit OC cells peritoneal dissemination.
  
  
  CONCLUSIONS
  Collectively, this study emphasized the importance of leptin in OC progression and illustrated a novel mechanism that the PI3K/Akt/mTOR pathway was involved in leptin-induced EMT. Our findings provide new insights into leptin exertion on OC metastasis and identify the potential of leptin neutralizing as a novel strategy against OC peritoneal dissemination.
authors.affiliation: Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Wei
authors.affiliation: Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Gong
authors.affiliation: Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Teng
authors.initials: T
authors.lastname: Ji
authors.affiliation: Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Xiaoshui
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Taoran
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Dongyi
authors.initials: D
authors.lastname: Wan
authors.affiliation: Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Sen
authors.initials: S
authors.lastname: Xu
authors.affiliation: Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Jin
authors.affiliation: Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Yang
authors.affiliation: Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Xiaoting
authors.initials: X
authors.lastname: Li
authors.affiliation: Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Ding
authors.initials: D
authors.lastname: Ma
authors.affiliation: Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Zongyuan
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Qinglei
authors.initials: Q
authors.lastname: Gao
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000077216:Carcinoma, Ovarian Epithelial; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005260:Female; D006801:Humans; D020738:Leptin / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D015394:Molecular Structure; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D020738:Leptin
keywords: EMT; Leptin; PI3K/Akt/mTOR; metastasis; ovarian cancer; therapeutic strategy