Loss of miR-200 family in XXXX resistant @entity694 drives lymphendothelial invasiveness in vitro.

@entity5 @entity600 @entity18075 @entity18076 @entity19099 @entity14 @entity694 @entity1487
UNASSIGNED: Invasive @entity14 is associated with poor prognosis requiring treatment with systemic chemotherapies usually including @entity1487 . A consequence of prolonged treatment is the acquisition of resistance eventually resulting in the recurrence of highly metastatic @entity5 cells. To address the relationship between drug resistance and increased lymphatic metastatic potential, we used a 3D co-culture model of @entity5 cell spheroids of parent CCL227 cells and subclones with gradually increasing resistance against @entity1487 . From each investigated cell line, homogeneous @entity5 spheroids were generated in the presence of methylcellulose yielding emboli of    700   m diameter. When invasive, @entity5 spheroids disrupt the continuous lymphendothelial cell (LEC) layer and generate a "circular chemorepellent induced defect" ( @entity600 ), reminiscent of the entry gates through which @entity5 emboli intravasate lymphatic vasculature. Here we provide evidence that increasingly chemoresistant @entity694 spheroids were strongly associated with enhanced intravasative properties. In na  ve CCL227 spheroids, miR-200 family members were released into exosomes thereby repressing the epithelial to mesenchymal transition-regulating transcription factors @entity18075 and @entity19099 in LEC. As a consequence of attenuated plasticity and migration of LEC, @entity600 formation was impaired. Loss of exosomal transferred @entity18076 in resistant colon cells rendered LEC more susceptible to pro-migratory signals that were generated and directly transmitted by @entity694 spheroids. This observation indicates a common molecular axis in @entity694 and LEC where miR-200 family members act as regulators of ZEB proteins. The data support the notion that horizontal miR-200 signalling prevents the permeation of cells into adjacent epithelia and contributes to organ integrity.
