(584c) Quantitative Analysis of Contact Inhibition of Locomotion During Fibrillar-Like Migration

Metastasis accounts for ninety percent of all cancer-related deaths. This process, driven by cell migration, involves cancer cells escaping from the primary tumor, invading the local tissue and forming secondary tumors in remote areas of the body. Healthy cells do not exhibit this ability because their locomotion is inhibited by contact with other cells. Contact inhibition of locomotion (CIL) is suppressed in cancer cells, one distinctive feature that allows them to become metastatic. In contrast to the 2D culture systems used to study CIL, cancer cells invade through a three-dimensional microenvironment composed of fibers[1]. These fibers are often composed of extracellular matrix proteins including fibronectin and collagen. To date, there has been no work to explore CIL in the context of fibrillar migration. To begin to examine the nature of CIL in confined, fibrillar-like microenvironments, we utilized 1D micropatterned surfaces as an analog to the 3D fibrillar environment in which tumor cells invade. Time-lapse microscopy was used to quantitatively compare homotypic CIL between normal mammary epithelial cells (MCF 10A) and metastatic breast cancer cells (MDA-MB-231). Cells were confined on patterned lines that varied in width from 6 to 33 microns. Pairwise interactions between cells were imaged in real-time and scored as bouncing or sliding collisions using frame-by-frame image analysis. The fraction of sliding collisions was measured as a representative metric of CIL and reported as a function of patterned line width. Our data reveal that cancer cells do overcome CIL even in confined 1D microenvironments. In fact, the ability of cancer cells to evade CIL is significantly enhanced in more confined 1D microenvironments, revealing that the migratory advantage of metastatic cells may be particularly well tuned to the spatial constraints of the local tumor microenvironment. These findings were statistically significant and confirmed this platform as a novel tool to quantitatively measure CIL ex vivo. The observed trend in the ability of metastatic cancer cells to undergo sliding collisions on thinner patterns would not have been found using traditional two-dimensional tissue culture dishes.

References:

[1]       P. P. P. Provenzano, BMC Med, 2006, vol. 4, pp. 38–38.