Tumor cell migration toward and intravasation into capillaries is an early and key event in cancer metastasis, yet not all cancer cells are imbued with the same capability to do so. This heterogeneity within a tumor is a fundamental property of cancer. Tools to help us understand what molecular characteristics allow a certain subpopulation of cells to spread from the primary tumor are thus critical for overcoming metastasis. Conventional in vitro migration platforms treat populations in aggregate, which leads to a masking of intrinsic differences among cells. Some migration assays reported recently have single-cell resolution, but these platforms do not provide for selective retrieval of the distinct migrating and non-migrating cell populations for further analysis. Thus, to study the intrinsic differences in cells responsible for chemotactic heterogeneity, we developed a single-cell migration platform so that individual cells' migration behavior can be studied and the heterogeneous population sorted based upon chemotactic phenotype. Furthermore, after migration, the highly chemotactic and non-chemotactic cells were retrieved and proved viable for later molecular analysis of their differences. Moreover, we modified the migration channel to resemble lymphatic capillaries to better understand how certain cancer cells are able to move through geometrically confining spaces.
Bibliographical noteFunding Information:
This work was supported in part by the: Department of Defense (W81XWH-12-1-0325), National Institute of Health (1R21CA17585701), National Cancer Institute F30 fellowship program (NIH/NCI 1F30CA173910-01A1), University of Michigan Rackham Predoctoral Fellowship (SGA), Breast Cancer Research Foundation, Avon Foundation, and the Metavivor Foundation. Use of the fabrication facilities at the Lurie Nanofabrication Facility of University of Michigan (Ann Arbor, MI) is greatly appreciated.
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