3-D Screens Predict Breast Cancer Metastasis

Cell-ECM Interactions

3-D culturing solutions and methods are increasingly being used to created more in vivo like assays.

Here researchers use our Human Collagen IV extracellular matrix protein (ECM) to develop a simple biomaterial platform with systematic control over the ECM protein density and composition to determine if integrin binding governs how metastatic cells differentiate between secondary tissue sites: L.E. Barney, E.C. Dandley, L.E. Jansen, N.G. Reich, A.M. Mercurio, and S.R. Peyton. A cell–ECM screening method to predict breast cancer metastasis. Integr Biol (Camb). 2015 Feb 10; 7(2): 198–212. doi: 10.1039/c4ib00218k.

This publication details the creation of an in vitro fingerprint that is predictive of in vivo metastasis.

Figure: Biomaterial platform for integrin-mediated phenotyping. (a) Breast cancer cell lines with their known in vivo metastatic tropisms.  (b) Three distinct ECM microenvironments regulate integrin binding. (c) Adhesion and motility phenotypes of the MDA-MB-231 cell line. Black: ECM 1; blue: ECM 2; green: ECM 3.

Figure: Correlations between adhesion and migration responses identify potent integrin antibodies in vitro. Pairwise comparisons between adhesion and migration measurements in the (a, b) MDA-MB-231 and (c, d) SkBr3 cell lines across normal, EGF-stimulated, and integrin antibody conditions. Arrows highlight conditions where integrin antibodies increased migration metrics. Spearman correlations are indicated on each plot with two-tailed p-values. Circle: ECM 1; square: ECM 2; triangle: ECM 3; black: normal; green: EGF; blue: anti-β1 integrin; red: anti-α2 integrin; orange: anti-α6 integrin. (e, f) SkBr3 migration mechanisms are displayed via 10 random cell paths under (e) normal and (f) anti-β1 conditions. Red paths identify cells detaching and adhering elsewhere on the surface. Inset: representative images of cell morphology. Scale bar is 25 μm. (g) Individual cells that invaded into an overlaid 3D collagen gel from the ECM 1 surface after 48 hours. Bar indicates mean distance invaded of all invading cells. Inset: schematic of cells invading upward from the ECM surface into an overlaid gel.

A richer understanding of cancer metastasis is important for the development of new, more potent chemotherapies. I am hopeful 3-D/ECM assays become more embraced as a way to more accuratly determine in vivo cell behaviors.