2D protrusion but not motility predicts growth factor-induced cancer cell migration in 3D collagen.

2D protrusion but not motility predicts growth factor-induced cancer cell migration in 3D collagen.
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DOI:
10.1083/jcb.201201003
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发表时间:
2012-06-11
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Lauffenburger DA
Lauffenburger DA
中科院分区:
其他
文献类型:
--
作者:
Meyer AS;Hughes-Alford SK;Kay JE;Castillo A;Wells A;Gertler FB;Lauffenburger DA

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In breast cancer cells, growth factor stimulation of membrane protrusion was a better predictor of 3D migration than 2D motility, cognate receptor expression, or receptor activation. Growth factor–induced migration is a critical step in the dissemination and metastasis of solid tumors. Although differences in properties characterizing cell migration on two-dimensional (2D) substrata versus within three-dimensional (3D) matrices have been noted for particular growth factor stimuli, the 2D approach remains in more common use as an efficient surrogate, especially for high-throughput experiments. We therefore were motivated to investigate which migration properties measured in various 2D assays might be reflective of 3D migratory behavioral responses. We used human triple-negative breast cancer lines stimulated by a panel of receptor tyrosine kinase ligands relevant to mammary carcinoma progression. Whereas 2D migration properties did not correlate well with 3D behavior across multiple growth factors, we found that increased membrane protrusion elicited by growth factor stimulation did relate robustly to enhanced 3D migration properties of the MDA-MB-231 and MDA-MB-157 lines. Interestingly, we observed this to be a more reliable relationship than cognate receptor expression or activation levels across these and two additional mammary tumor lines.
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