Noninvasive MRI of Endothelial Cell Response to Human Breast Cancer Cells

Abstract

We have developed a noninvasive magnetic resonance imaging (MRI) assay to characterize human umbilical vein endothelial cell (HUVEC) motility, invasion, and network formation in response to the presence of cancer cells. HUVECs were labeled with a superparamagnetic iron oxide T2 contrast agent and cocultured with MDAMB-231 breast cancer cells in the presence of an extracellular matrix (ECM) gel. Invasion into the ECM gel by HUVECs in response to paracrine factors secreted by MDA-MB-231 cancer cells, as well as network formation by HUVECs, was easily tracked with MRI. The invasive behavior of HUVECs was not observed in the absence of cancer cells. This noninvasive assay used to characterize the response of endothelial cells (ECs) can be used to understand the role of proangiogenic or antiangiogenic stimuli, and to study the interactions between ECs and other disease-specific cells in pathologies with aberrant angiogenesis, such as retinopathy and arthritis.