Discriminating expression of differentiation markers evolves in transplants of benign and malignant XXXX skin keratinocytes through stromal interactions.

@entity1 @entity4166 @entity5 @entity19 @entity189 @entity7435 @entity2277 @entity218
Accumulating evidence indicates a decisive role for the adjacent stroma in @entity5 growth and dissemination. However, it is not clear how far altered differentiation such as expression of aberrant keratins and @entity2277 , common in invasive @entity1 @entity189 , may reflect intrinsic cell properties or a response to the @entity5 environment. We have addressed this by transplanting benign and malignant @entity1 HaCaT-ras keratinocytes, seeded on collagen matrix, onto @entity19 . Initially, epithelia derived from benign and malignant cells, being separated from host stroma by collagen, were poorly organized and exhibited the same differentiation markers, as identified by immunofluorescence and in situ hybridization. Epidermal basal and suprabasal keratins were expressed persistently even upon contact with newly formed stroma and malignant cell invasion. In contrast, non-epidermal keratins (K4/ @entity7435 , K8/18, @entity4166 ), which were similarly synthesized by benign and malignant cells in culture and in early transplants, were differentially regulated with increasing stromal vicinity. While both proteins and mRNAs were downregulated in benign epithelia, the malignant, invasive @entity5 cells continuously expressed these non-epidermal keratins throughout ( @entity4166 ), suprabasally ( @entity218 ) or at invasive sites (K8/18). Furthermore, the mesenchymal protein @entity2277 was expressed de novo in invasive areas confronting @entity5 stroma. Thus, atypical tissue markers, similarly synthesized in isolated cells in vitro, are downregulated in benign but maintained and upregulated in malignant epithelia. This is presumably caused by the neighbouring stroma being permanently activated by malignant epithelia.
