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Doctoral Thesis
DOI
10.11606/T.5.2017.tde-06032017-104147
Document
Author
Full name
Guilherme Tude Coelho Neto
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2016
Supervisor
Committee
Silva, Fabiano Pinheiro da (President)
Taniguchi, Leandro Utino
Barbeiro, Hermes Vieira
Machado, Marcel Cerqueira Cesar
Severino, Patrícia
Title in Portuguese
Peptídeo antimicrobiano LL-37 e seus efeitos em stemness de diferentes células tumorais
Keywords in Portuguese
Catelicidinas
Expressão gênica
Fenômenos do sistema imunológico
Imunidade inata
Melanoma
Neoplasias cutâneas
Neoplasias da mama
Peptídeos catiônicos antimicrobianos
RNA interferente pequeno
Técnicas de silenciamento de genes
Abstract in Portuguese
Os peptídeos antimicrobianos desempenham papéis protetores críticos em uma gama de doenças humanas, incluindo o câncer. Vários estudos demonstraram funções - tais como proliferação, angiogênese, apoptose e imunomodulação - desses peptídeos em vias cancerígenas cruciais. Investigamos o papel do Peptídeo antimicrobiano LL-37 sobre stemness em câncer de mama (SKBR3) e células de melanoma (A375). Análise por PCR array da expressão diferencial de genes em SKBR3 e A375 com knockdown por siRNA para o mRNA de LL-37 revelou uma regulação negativa de genes relacionados com stemness, incluindo transcriptase reversa da telomerase, forkhead box D3 e para o fator indiferenciado de transcrição de células embrionárias 1, notavelmente em células de câncer de mama.Além disso, as células SKBR3 com knockdown para a expressão de LL-37 mostraram uma diminuição da produção de oncosferas em comparação com controles negativos, enquanto as células A375 exibiram uma produção aumentada. Tomados em conjunto, nossos achados indicam um papel para LL- 37 em stemness, dependendo do tipo de celular analisado
Title in English
Antimicrobial peptide LL-37 and its effects on stemness in different cancer cells
Keywords in English
Antimicrobial cationic peptides
Breast neoplasms
Cathelicidins
Gene expression
Gene knockdown techniques
Immune system phenomena
Immunity innate
Melanoma
RNA small interfering
Skin neoplasms
Abstract in English
Antimicrobial peptides play critical protective roles in a range of human diseases, including cancer. Multiple studies have demonstrated functions -- such as proliferation, angiogenesis, apoptosis and immunomodulation -- of these peptides in crucial cancer pathways. We investigated the role of the antimicrobial peptide LL-37 on stemness in breast cancer (SKBR3) and melanoma cells (A375). PCR array analysis of differential gene expression in SKBR3 and A375 cancer cell lines downregulated for LL-37 expression by siRNA revealed downregulation of genes related to stemness, including telomerase reverse transcriptase, forkhead box D3 and undifferentiated embryonic cell transcription factor 1, remarkably in breast cancer cells. Furthermore, SKBR3 cells knocked down for LL-37 expression showed a decreased production of oncospheres in comparison with negative controls, while A375 cells exhibited increased production. Taken collectively, our findings indicate a role for LL-37 in cancer cell stemness depending on the cell type
 
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Publishing Date
2017-03-06
 
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