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PLoS One ; 5(11): e14131, 2010 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-21152434

RESUMO

BACKGROUND: Mounting clinical and experimental evidence suggests that the shift of carcinomas towards a mesenchymal phenotype is a common paradigm for both resistance to therapy and tumor recurrence. However, the mesenchymalization of carcinomas has not yet entered clinical practice as a crucial diagnostic paradigm. METHODOLOGY/PRINCIPAL FINDINGS: By integrating in silico and in vitro studies with our epithelial and mesenchymal tumor models, we compare herein crucial molecular pathways of previously described carcinoma-derived mesenchymal tumor cells (A17) with that of both carcinomas and other mesenchymal phenotypes, such as mesenchymal stem cells (MSCs), breast stroma, and various types of sarcomas. We identified three mesenchymal/stromal-signatures which A17 cells shares with MSCs and breast stroma. By using a recently developed computational approach with publicly available microarray data, we show that these signatures: 1) significantly relates to basal-like breast cancer subtypes; 2) significantly relates to bone metastasis; 3) are up-regulated after hormonal treatment; 4) predict resistance to neoadjuvant therapies. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that mesenchymalization is an intrinsic property of the most aggressive tumors and it relates to therapy resistance as well as bone metastasis.


Assuntos
Neoplasias Ósseas/genética , Neoplasias da Mama/genética , Perfilação da Expressão Gênica , Mesoderma/metabolismo , Células Estromais/metabolismo , Animais , Western Blotting , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Análise por Conglomerados , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Células Epiteliais/metabolismo , Feminino , Humanos , Células-Tronco Mesenquimais/metabolismo , Mesoderma/patologia , Camundongos , Terapia Neoadjuvante/métodos , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais , Células Estromais/patologia
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