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Additionally, the regulation of certain metastasis-related genes also modulates the occurrence and burden of metastases.
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The study of the intravasation step has been hampered though by the lack of accessible in vitro techniques. One such rate-limiting step is the chemotactic migration and intravasation of tumor cells from the tumor stroma to a capillary bed or lymphatic vessels 1, 2, 3, 4. Cancer metastases result from a multi-step process with significant attrition of viable cells at each step in the metastatic cascade. In particular, significant attention has been paid to the migration of cancer cells since cancer metastases account for more than 90% of cancer-related mortality 1, 2.
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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.Ĭell migration is an essential process in angiogenesis, cancer metastasis, wound healing, inflammation and embryogenesis. Furthermore, after migration, the highly chemotactic and non-chemotactic cells were retrieved and proved viable for later molecular analysis of their differences. 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. 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. Conventional in vitro migration platforms treat populations in aggregate, which leads to a masking of intrinsic differences among cells. 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. This heterogeneity within a tumor is a fundamental property of cancer. 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.