Leptin acts on neoplastic behavior and expression levels of genes related to hypoxia, angiogenesis, and invasiveness in oral squamous cell carcinoma

Leptin, one of the main hormones controlling energy homeostasis, has been associated with different cancer types. In oral cancer, its effect is not well understood. We investigated, through in vitro and in vivo assays, whether leptin can affect the neoplastic behavior of oral squamous cell carcinoma...

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Main Authors: Eliane Macedo Sobrinho Santos, Talita Antunes Guimarães, Hércules Otacílio Santos, Lilian Mendes Borborema Cangussu, Sabrina Ferreira de Jesus, Carlos Alberto de Carvalho Fraga, Claudio Marcelo Cardoso, Sérgio Henrique Souza Santos, Alfredo Maurício Batista de Paula, Ricardo Santiago Gomez, André Luiz Sena Guimarães, Lucyana Conceição Farias
Format: Article
Language:English
Published: SAGE Publishing 2017-04-01
Series:Tumor Biology
Online Access:https://doi.org/10.1177/1010428317699130
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author Eliane Macedo Sobrinho Santos
Talita Antunes Guimarães
Hércules Otacílio Santos
Lilian Mendes Borborema Cangussu
Sabrina Ferreira de Jesus
Carlos Alberto de Carvalho Fraga
Claudio Marcelo Cardoso
Sérgio Henrique Souza Santos
Alfredo Maurício Batista de Paula
Ricardo Santiago Gomez
André Luiz Sena Guimarães
Lucyana Conceição Farias
author_facet Eliane Macedo Sobrinho Santos
Talita Antunes Guimarães
Hércules Otacílio Santos
Lilian Mendes Borborema Cangussu
Sabrina Ferreira de Jesus
Carlos Alberto de Carvalho Fraga
Claudio Marcelo Cardoso
Sérgio Henrique Souza Santos
Alfredo Maurício Batista de Paula
Ricardo Santiago Gomez
André Luiz Sena Guimarães
Lucyana Conceição Farias
author_sort Eliane Macedo Sobrinho Santos
collection DOAJ
description Leptin, one of the main hormones controlling energy homeostasis, has been associated with different cancer types. In oral cancer, its effect is not well understood. We investigated, through in vitro and in vivo assays, whether leptin can affect the neoplastic behavior of oral squamous cell carcinoma. Expression of genes possibly linked to the leptin pathway was assessed in leptin-treated oral squamous cell carcinoma cells and also in tissue samples of oral squamous cell carcinoma and oral mucosa, including leptin, leptin receptor, hypoxia-inducible factor 1-alpha, E-cadherin, matrix metalloproteinase-2, matrix metalloproteinase-9, Col1A1, Ki67, and mir-210. Leptin treatment favored higher rates of cell proliferation and migration, and reduced apoptosis. Accordingly, leptin-treated oral squamous cell carcinoma cells show decreased messenger RNA caspase-3 expression, and increased levels of E-cadherin, Col1A1, matrix metalloproteinase-2, matrix metalloproteinase-9, and mir-210. In tissue samples, hypoxia-inducible factor 1-alpha messenger RNA and protein expression of leptin and leptin receptor were high in oral squamous cell carcinoma cases. Serum leptin levels were increased in first clinical stages of the disease. In animal model, oral squamous cell carcinoma–induced mice show higher leptin receptor expression, and serum leptin level was increased in dysplasia group. Our findings suggest that leptin seems to exert an effect on oral squamous cell carcinoma cells behavior and also on molecular markers related to cell proliferation, migration, and tumor angiogenesis.
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spelling doaj-art-68cd9d2e065d48c7a9475eec962615ab2025-08-20T03:33:50ZengSAGE PublishingTumor Biology1423-03802017-04-013910.1177/1010428317699130Leptin acts on neoplastic behavior and expression levels of genes related to hypoxia, angiogenesis, and invasiveness in oral squamous cell carcinomaEliane Macedo Sobrinho Santos0Talita Antunes Guimarães1Hércules Otacílio Santos2Lilian Mendes Borborema Cangussu3Sabrina Ferreira de Jesus4Carlos Alberto de Carvalho Fraga5Claudio Marcelo Cardoso6Sérgio Henrique Souza Santos7Alfredo Maurício Batista de Paula8Ricardo Santiago Gomez9André Luiz Sena Guimarães10Lucyana Conceição Farias11Instituto Federal do Norte de Minas Gerais–Campus Araçuaí, Montes Claros, BrazilDepartment of Dentistry, Universidade Estadual de Montes Claros, Montes Claros, BrazilDepartment of Biotechnology, Universidade de São Paulo (USP), São Paulo, BrazilDepartment of Dentistry, Universidade Estadual de Montes Claros, Montes Claros, BrazilDepartment of Dentistry, Universidade Estadual de Montes Claros, Montes Claros, BrazilDepartment of Dentistry, Universidade Estadual de Montes Claros, Montes Claros, BrazilDepartment of Dentistry, Universidade Estadual de Montes Claros, Montes Claros, BrazilInstitute of Agricultural Sciences, Food Engineering College, Universidade Federal de Minas Gerais (UFMG), Montes Claros, Minas Gerais, BrazilDepartment of Dentistry, Universidade Estadual de Montes Claros, Montes Claros, BrazilDepartment of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, BrazilDepartment of Dentistry, Universidade Estadual de Montes Claros, Montes Claros, BrazilDepartment of Dentistry, Universidade Estadual de Montes Claros, Montes Claros, BrazilLeptin, one of the main hormones controlling energy homeostasis, has been associated with different cancer types. In oral cancer, its effect is not well understood. We investigated, through in vitro and in vivo assays, whether leptin can affect the neoplastic behavior of oral squamous cell carcinoma. Expression of genes possibly linked to the leptin pathway was assessed in leptin-treated oral squamous cell carcinoma cells and also in tissue samples of oral squamous cell carcinoma and oral mucosa, including leptin, leptin receptor, hypoxia-inducible factor 1-alpha, E-cadherin, matrix metalloproteinase-2, matrix metalloproteinase-9, Col1A1, Ki67, and mir-210. Leptin treatment favored higher rates of cell proliferation and migration, and reduced apoptosis. Accordingly, leptin-treated oral squamous cell carcinoma cells show decreased messenger RNA caspase-3 expression, and increased levels of E-cadherin, Col1A1, matrix metalloproteinase-2, matrix metalloproteinase-9, and mir-210. In tissue samples, hypoxia-inducible factor 1-alpha messenger RNA and protein expression of leptin and leptin receptor were high in oral squamous cell carcinoma cases. Serum leptin levels were increased in first clinical stages of the disease. In animal model, oral squamous cell carcinoma–induced mice show higher leptin receptor expression, and serum leptin level was increased in dysplasia group. Our findings suggest that leptin seems to exert an effect on oral squamous cell carcinoma cells behavior and also on molecular markers related to cell proliferation, migration, and tumor angiogenesis.https://doi.org/10.1177/1010428317699130
spellingShingle Eliane Macedo Sobrinho Santos
Talita Antunes Guimarães
Hércules Otacílio Santos
Lilian Mendes Borborema Cangussu
Sabrina Ferreira de Jesus
Carlos Alberto de Carvalho Fraga
Claudio Marcelo Cardoso
Sérgio Henrique Souza Santos
Alfredo Maurício Batista de Paula
Ricardo Santiago Gomez
André Luiz Sena Guimarães
Lucyana Conceição Farias
Leptin acts on neoplastic behavior and expression levels of genes related to hypoxia, angiogenesis, and invasiveness in oral squamous cell carcinoma
Tumor Biology
title Leptin acts on neoplastic behavior and expression levels of genes related to hypoxia, angiogenesis, and invasiveness in oral squamous cell carcinoma
title_full Leptin acts on neoplastic behavior and expression levels of genes related to hypoxia, angiogenesis, and invasiveness in oral squamous cell carcinoma
title_fullStr Leptin acts on neoplastic behavior and expression levels of genes related to hypoxia, angiogenesis, and invasiveness in oral squamous cell carcinoma
title_full_unstemmed Leptin acts on neoplastic behavior and expression levels of genes related to hypoxia, angiogenesis, and invasiveness in oral squamous cell carcinoma
title_short Leptin acts on neoplastic behavior and expression levels of genes related to hypoxia, angiogenesis, and invasiveness in oral squamous cell carcinoma
title_sort leptin acts on neoplastic behavior and expression levels of genes related to hypoxia angiogenesis and invasiveness in oral squamous cell carcinoma
url https://doi.org/10.1177/1010428317699130
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