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Doctoral Thesis
DOI
https://doi.org/10.11606/T.17.2019.tde-15102018-115244
Document
Author
Full name
Fernanda Marques Rey
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
Ribeirão Preto, 2018
Supervisor
Committee
Tiezzi, Daniel Guimarães (President)
Derchain, Sophie Françoise Mauricette
Baqui, Munira Muhammad Abdel
Pereira, Julia Santucci
Reis, Francisco José Cândido dos
Title in Portuguese
Interação de célula tronco mesenquimal com células de linhagem do câncer de mama e avaliação de seu comportamento biológico
Keywords in Portuguese
Câncer de mama
Célula tronco mesenquimal
Expansão clonal
MCF- 7
Abstract in Portuguese
O câncer de mama é uma doença heterogênea que é caracterizada por células epiteliais de mama malignas. As células-tronco cancerígenas (CST) no câncer de mama podem aumentar o potencial de agressividade através do tumor. O objetivo deste estudo é avaliar a expansão clonal do microambiente tumoral e a diferenciação celular após o estímulo com células estaminais mesenquimais. As células MSC derivadas da geléia de Wharton foram co-cultivadas com MCF- 7 em proporções de 1%, 10%, 30%. A co-cultura de MCF-7 com MSC mostrou alteração na localização da e-caderina para o citoplasma e, de preferência, o núcleo. Para a n-caderina, a co-localização foi predominantemente na membrana após a exposição do MSC. As células MCF-7 apresentaram colocalização do citoplasma e do núcleo no biomarcador de ?-catenina. Este fenômeno é confirmado à WB com o aumento dos níveis de proteínas de ecaderina no citoplasma no MCF-7 após o estímulo do MSC. A morfologia das transições amênico-mesenquimatosas foi mostrada no ensaio 3D em algumas colônias, no entanto esta morfologia não é predominante. A co-cultura de MCF- 7 com MSCs aumenta o número de mammosferes e influencia o aumento de CD44 + / CD24-, esse fenômeno foi possível sob estimulação de 30% das células MSC. A linhagem celular de câncer de mama MCF-7 em associação com MSC pode aumentar o potencial de agressividade através do tumor. Essa interação no microambiente do tumor é determinante para a expansão clonal e diferenciação celular, que são mecanismos relevantes no processo de disseminação metastática.
Title in English
Interaction of mesenchymal stem cell with breast cancer lineage cells and evaluation of their biological behavior
Keywords in English
Breast cancer
Clonal expansion
MCF-7
Mesenchymal stem cells
Abstract in English
Breast cancer is a heterogeneous disease that is characterized by malignant breast epithelial cells. Cancer stem cells (CST) in breast cancer can boost a potential for aggressiveness trough the tumor. The goal for this study is to evaluated the tumor microenvironment clonal expansion and cellular differentiation after stimulus with mesenchymal stem cells. MSC cells derived from Wharton's jelly were co-cultured with MCF-7 in proportions 1%,10%,30%. The co-culture of MCF-7 with MSC showed alteration on localization of ecadherin to the cytoplasm and preferably nucleus. For n-cadherin, the colocalization were predominantly in membrane after MSC exposition. MCF-7 cells showed cytoplasm and nucleus co-localization on ?-catenin biomarker. This phenomenon is confirmed to WB with increasing the proteins levels of ecadherin on cytoplasm in MCF-7 after MSC stimulus. Amoeboid to mesenchymal transitions morphology were showed on 3D assay in some colonies, however this morphology is not predominant. The co-culture of MCF-7 with MSCs increase in the number of mammospheres and influence the increase of CD44+/CD24-, this phenomenon was possible under stimulation of 30% of MSC cells. The breast cancer cell line MCF-7 in association with MSC can boost a potential for aggressiveness trough the tumor. This interaction on tumor microenvironment is determinant for the clonal expansion and cellular differentiation, which are relevant mechanisms in the process of metastatic dissemination.
 
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Publishing Date
2019-07-19
 
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