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Chemotaxis of Metastatic Breast Cancer Cells in Parallel Gradient Microfluidic Chambers

W. Saadi, S-J Wang, F. Lin and N.L. Jeon
University of California, Irvine, US

Keywords:
microfluidics, metastasis, breast cancer, chemotaxis, epidermal growth factor, inhibitors

Abstract:
Chemotaxis plays a key role in cancer metastasis, directing the motility of metastatic cells through gradients of growth factors or other chemoattractants. In order to rigorously characterize the role of growth factors in cancer cell chemotaxis, real-time observation of cell migration in stable growth factor gradients is required. Using microfluidic chambers to generate precise concentration gradients, we are able to study the migration of the human metastatic breast cancer cell line MDA-MB-231 in response to Epidermal growth factor (EGF). Real-time imaging of migrating cells allows quantitative analysis of chemotactic responses. In order to accurately characterize the influence of growth factor cues on breast caner cell migration, we developed a parallel-gradient microfluidic chamber capable of generating different gradients side by side. Applying this approach, we showed that EGF gradients induce directional migration of cancer cells; targeting the EGF receptor (EGFR) with an antibody (anti-EGFR) inhibits this chemotactic response. We also compared two different concentration ranges of EGF and observed subtle differences in the migration patterns. This parallel-gradient microfluidic chamber provides an engineering approach for sensitive comparisons between different conditions in a manner that is highly controlled yet relevant to metastasis.

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