Intravital Imaging Reveals Transient Changes in Pigment Production and Brn2 Expression during Metastatic Melanoma Dissemination

摘要: How melanoma acquire a metastatic phenotype is key issue. One possible mechanism that metastasis driven by microenvironment-induced switching between noninvasive and invasive states. However, whether reversible or hierarchical process not known difficult to assess comparison of primary tumors. We address this issue in model using novel intravital imaging method for melanosomes combined with reporter construct which the Brn-2 promoter drives green fluorescent protein (GFP) expression. A subpopulation cells containing little no pigment high levels Brn2::GFP expression are motile tumor enter vasculature. Significantly, less differentiated state intravasated maintained at secondary sites, implying states as metastasize. show can switch both directions high- low-pigment from low was greatly favored over reverse direction. Microarray analysis populations revealed transforming growth factor (TGF)beta2 up-regulated poorly pigmented cells. Furthermore, TGFbeta signaling induced hypopigmentation increased cell motility. Thus, subset exits but subsequently give rise metastases include range more pigment-producing These data during metastasis.