Figure 3.
Effects of transduced BMP7 on melanoma growth and invasion in 3D skin reconstructs. In susceptible primary melanoma cell line WM793, Ad/GFP-infected cells grow as large nests and single cells within the epidermis (*) and superficial dermis (#; A). Upon BMP7-transduction, WM793 cells show small clusters as well as single units at the dermal epidermal junction (B, ^) reactive to TUNNEL stain (F, ^). GFP tranfectants of the relative resistant isogenic cell line 1205Lu grow aggressively forming large tumor nests in the deep dermis (C, #), while the BMP7-transfectants (D, #) displayed extensive cell death (^) with morphological hallmarks of apoptosis (D and E, ^). Control GFP-transfected susceptible metastatic C81-61 melanoma cells grow aggressively as large nests and nodules within the dermis (G, #), whereas their BMP7-transduced counterparts only show small remnants of dermal tumor nests (H, #). In the resistant, highly aggressive C8161 melanoma cells, both Ad/GFP- (I) and Ad/BMP7-infected cells (J) grow aggressively into the dermis (#) and eventually also replace the epidermis with rare residual keratinocyte islands (I, J, *).