Abstract
The chemokine receptor CXCR4 and its ligand CXCL12 play an important role in breast cancer invasion and metastasis, and induce the chemotaxis of various types of cancer cells. Previous studies of CXCL12βinduced chemotaxis have, for the most part, relied on endpoint assays (e.g., transwell assays) that provide poor control over the cell microenvironment. Specifically, these assays lacked the ability to dissect the role that autocrine and paracrine growth factors play in chemokineβinduced cancer cell chemotaxis. Here, we employ a microfluidic chemotaxis chamber that allows the effects of specific exogenous factors on cell migration to be directly characterized, without the interference of autocrine/paracrine signaling. Using this approach, we investigated the migration of MDAβMBβ231 breast cancer cells in wellβdefined CXCL12 gradients. We found that CXCL12 alone failed to stimulate chemotaxis of these cells; however, when the CXCL12 gradient was supplemented with a uniform stimulus of either EGF or conditioned media, a directional response was induced. This dependence on growth factor signaling points to the importance of autocrine and paracrine factors in determining the migratory response of the cells, and may play an important role in cancer metastasis. Biotechnol. Bioeng. 2008;100: 1205β1213. Β© 2008 Wiley Periodicals, Inc.