A dynamic in vivo model of epithelial-to-mesenchymal transitions in circulating XXXX cells and metastases of @entity0 .

@entity1 @entity12848 @entity4245 @entity0 @entity5 @entity5962 @entity19099 @entity2277 @entity17264 @entity49713 @entity2880
Epithelial-to-mesenchymal transition (EMT) processes endow epithelial cells with enhanced migratory/invasive properties and are therefore likely to contribute to @entity5 invasion and metastatic spread. Because of the difficulty in following EMT processes in @entity1 @entity5 , we have developed and characterized an animal model with transplantable @entity1 @entity0 cells (MDA-MB-468) uniquely showing spontaneous EMT events to occur. Using @entity2277 as a marker of EMT, heterogeneity was revealed in the primary MDA-MB-468 xenografts with @entity2277 -negative and @entity2277 -positive areas, as also observed on clinical @entity1 invasive @entity0 specimens. Reverse transcriptase-PCR after microdissection of these populations from the xenografts revealed EMT traits in the @entity2277 -positive zones characterized by enhanced 'mesenchymal gene' expression ( @entity4245 , @entity19099 and @entity12848 ) and diminished expression of epithelial molecules ( @entity5962 , @entity49713 and @entity17264 ). Circulating @entity5 cells (CTCs) were detected in the blood as soon as 8 days after s.c. injection, and lung metastases developed in all animals injected as examined by in vivo imaging analyses and histology. High levels of @entity2277 RNA were detected in CTCs by reverse transcriptase-quantitative PCR as well as, to a lesser extent, @entity4245 and @entity19099 RNA. @entity2880 Factor/ @entity2277 double immunostainings further showed that @entity5 cells in vascular tumoral emboli all expressed @entity2277 . Tumoral emboli in the lungs also expressed @entity2277 whereas macrometastases displayed heterogenous @entity2277 expression, as seen in the primary xenografts. In conclusion, our data uniquely demonstrate in an in vivo context that EMT occurs in the @entity5 , and associates with an enhanced ability to intravasate and generate CTCs. They further suggest that mesenchymal-to-epithelial phenomena occur in secondary organs, facilitating the metastatic growth.
