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Physical limits of cell migration

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If you have a question about this talk, please contact Katrien Van Look .

Cancer cell invasion into interstitial tissue is a key step to cancer progression and metastasis. Cell surface proteases facilitate proteolytic invasion. Upon MMP inhibitor treatment, cancer cells may switch to nonproteolytic compensatory movement or stop to migrate, yet the tissue conditions that facilitate or prevent non-proteolytic migration remain unknown. We here define the mechanisms and physical limits of protease-independent migration, using spatially controlled 3D fibrillar lattices of non-crosslinked macroporous or cross-linked microporous collagen. In addition, pore size within the same collagen preparation was modified by density titration or assembly speed variation. Consistent with gap diameters, cancer cells maintained after MMP inhibition amoeboid nuclear squeezing in macroporous lattices, whereas microporous networks forced migration arrest. Thus, rather than the presence or absence of cross-links, the physical dimensions of ECM gaps and pores control nuclear morphology, and therefore efficiency and protease requirements of cancer cell migration.

This talk is part of the Cancer Research UK Cambridge Institute (CRUK CI) Seminars in Cancer series.

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