title: A novel three-dimensional model to quantify metastatic melanoma invasion.
abstract: Although attempts to develop any viable chemotherapeutic approaches to combat metastatic cancers have largely failed, potential genetic targets to halt metastatic progression continue to be identified. As drugs are developed to address these targets, there is a need for high-throughput systems that accurately reproduce in vivo microenvironments to gauge their efficacy. Accordingly, we have developed a three-dimensional in vitro culture system representative of the environment present upon secondary metastasis to quantitatively measure tumor cell invasion in this setting three-dimensionally. Culturing melanomas of different metastatic capacities within the system showed that each cell type invades the matrix in a manner commensurate to its known metastatic potential in vivo. Moreover, the developed quantitative schemes were put to use to characterize the effect of microenvironmental influences (i.e., matrix components, interstitial cell presence) on planar and vertical melanoma invasion. We propose this novel, quantitative system as a useful tool to assess the effects of pharmacologic and/or microenvironmental influences on tumor cell invasion at a metastatic site.
authors.affiliation: Department of Biomedical Engineering, 3120 Natural Sciences II, University of California-Irvine, Irvine, CA 92697-2715, USA.
authors.forename: Cyrus M
authors.initials: CM
authors.lastname: Ghajar
authors.forename: Vinod
authors.initials: V
authors.lastname: Suresh
authors.forename: Shelly R
authors.initials: SR
authors.lastname: Peyton
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Raub
authors.forename: Frank L
authors.initials: FL
authors.lastname: Meyskens
authors.forename: Steven C
authors.initials: SC
authors.lastname: George
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Putnam
mesh_terms: D003094:Collagen / Q000378:metabolism; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D005337:Fibrin / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008545:Melanoma / Q000503:physiopathology*; D008954:Models, Biological; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D012878:Skin Neoplasms / Q000503:physiopathology*
chemical_list: C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D005337:Fibrin; D003094:Collagen