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Research Articles: Therapeutics, Targets, and Development

A novel three-dimensional model to quantify metastatic melanoma invasion

Departments of ¹ Biomedical Engineering, ² Chemical Engineering and Materials Science, University of California-Irvine, Irvine, California; ³ Chao Family Comprehensive Cancer Center, Departments of ⁴ Medicine and ⁵ Biological Chemistry, University of California-Irvine School of Medicine, Orange, California

Requests for reprints: Andrew Putnam, Department of Biomedical Engineering, 3120 Natural Sciences II, University of California-Irvine, Irvine, CA 92697-2715. Phone: 949-824-1243; Fax: 949-824-1727. E-mail: aputnam{at}uci.edu

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. [Mol Cancer Ther 2007;6(2):552–61]

Grant support: University of California-Irvine's Council on Research, Computing and Library Resources (A.J. Putnam), setup funds from the University of California-Irvine (A.J. Putnam), and grant R01 HL067954 from the NIH (S.C. George). Partially supported by fellowships from the Achievement Rewards for College Scientists Foundation (in conjunction with the Arnold & Mabel Beckman Foundation for C.M. Ghajar) (C.M. Ghajar and S.R. Peyton).

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 9/25/06; revised 11/29/06; accepted 12/21/06.

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