RESUMO
BACKGROUND: Bone metastases represent a common and severe complication in breast cancer, and the involvement of cancer stem cells (CSCs) in the promotion of bone metastasis is currently under discussion. Here, we used a human-in-mice model to study bone metastasis formation due to primary breast CSCs-like colonisation. METHODS: Primary CD44âºCD24â» breast CSCs-like were transduced by a luciferase-lentiviral vector and injected through subcutaneous and intracardiac (IC) routes in non-obese/severe-combined immunodeficient (NOD/SCID) mice carrying subcutaneous human bone implants. The CSCs-like localisation was monitored by in vivo luciferase imaging. Bone metastatic CSCs-like were analysed through immunohistochemistry and flow cytometry, and gene expression analyses were performed by microarray techniques. RESULTS: Breast CSCs-like colonised the human-implanted bone, resulting in bone remodelling. Bone metastatic lesions were histologically apparent by tumour cell expression of epithelial markers and vimentin. The bone-isolated CSCs-like were CD44â»CD24⺠and showed tumorigenic abilities after injection in secondary mice. CD44â»CD24⺠CSCs-like displayed a distinct bone tropism signature that was enriched in genes that discriminate bone metastases of breast cancer from metastases at other organs. CONCLUSION: Breast CSCs-like promote bone metastasis and display a CSCs-like bone tropism signature. This signature has clinical prognostic relevance, because it efficiently discriminates osteotropic breast cancers from tumour metastases at other sites.
Assuntos
Neoplasias Ósseas/secundário , Osso e Ossos/metabolismo , Neoplasias da Mama/patologia , Carcinoma/patologia , Células-Tronco Neoplásicas/patologia , Transcriptoma , Adulto , Animais , Neoplasias Ósseas/genética , Osso e Ossos/patologia , Neoplasias da Mama/genética , Carcinoma/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Genes de Troca/genética , Humanos , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Células-Tronco Neoplásicas/metabolismo , Especificidade de Órgãos/genética , Fenótipo , Transcriptoma/fisiologiaRESUMO
The authors have administered a test of intelligence (WAIS) and a test of attention (Color Naming) to a group of patients affected by chronic schizophrenic impairment. The scores give shape to a picture of mental deterioration, especially characterized by a decrease of attentive power. This results validates the possibility of a neuropsychological approach to the etiopatogenesis of schizophrenia and supports the hypothesis that an impairment of mental synthesis power may explain both clinical and psychometric features of the disease.