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 threedimensionally. 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.

The Combined Influence of Hydrogel Stiffness and Matrix‐Bound Hyaluronic Acid Content on Glioblastoma Invasion

“…We employ a bead assay where GBM cells are first seeded onto Dextran beads coated in denatured collagen; cell‐coated beads are then encapsulated within the hydrogel, with the bead surface providing an accurate starting point for GBM invasion into the surrounding hydrogel. Research groups studying in vitro vascular network formation and the kinetics of melanoma invasion have previously reported the use of commercially available beads for cell‐bead‐hydrogel cocultures, though typically with less defined hydrogel carriers (e.g., fibrin, collagen) . While those approaches typically employ total spread area as a metric of cell spreading, we quantify cell invasion distance of each cell from the surface of the bead over extended culture (up to 7 d) times.…”

3D printing of biomimetic microstructures for cancer cell migration

“…(Jenkinson et al 2004),(Yamada and Cukierman 2007),(Watson et al 1995) 2D in vitro migration studies have used approaches such as microcarrier bead assays as well as a monolayer wound model. (Decaestecker et al 2007),(Ghajar et al 2007),(Mathew et al 1997),(Chaffer et al 2006) In addition, single-cell locomotion assays have proven useful in separating cell migration from cell growth. (Decaestecker et al 2007),(Albrecht-Buehler 1977) Recent studies on 3D in vitro migration systems provide more understanding of cell migration.…”

Tumor Engineering: The Other Face of Tissue Engineering

“…Studying tumors in 3D has proven far more accurate in reproducing in vivo growth characteristics and chemotherapeutic resistance than 2D approaches. 11,[15][16][17][18][19][20][21] A number of animal studies and co-culture experiments have identified also the importance of interactions with other nonmalignant cell types-such as endothelial cells, 22 fibroblasts, 11,21,23 adipocytes, 24 leukocytes, [25][26][27] and circulating progenitors 28,29 -to…”