Research Articles: Therapeutics, Targets, and Development

A novel three-dimensional model to quantify metastatic melanoma invasion

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

^* To whom correspondence should be addressed. 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):OF1-10]

Key Words: Tumor invasion and metastasis model, Melanoma, Cell-matrix interactions, Tumor-stromal cell interactions, Pharmacologic screening

This article has been cited by other articles:

				C. B. Raub, J. Unruh, V. Suresh, T. Krasieva, T. Lindmo, E. Gratton, B. J. Tromberg, and S. C. George Image Correlation Spectroscopy of Multiphoton Images Correlates with Collagen Mechanical Properties Biophys. J., March 15, 2008; 94(6): 2361 - 2373. [Abstract] [Full Text] [PDF]