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

Title2D protrusion but not motility predicts growth factor-induced cancer cell migration in 3D collagen.
Publication TypeJournal Article
Year of Publication2012
AuthorsMeyer, AS, Hughes-Alford, SK, Kay, JE, Castillo, A, Wells, A, Gertler, FB, Lauffenburger, DA
JournalJ Cell Biol
Date Published2012 Jun 11
KeywordsAnimals, Breast Neoplasms, Cell Line, Tumor, Cell Movement, Cell Proliferation, Collagen, Female, Humans, Intercellular Signaling Peptides and Proteins, Ligands, Neoplasms, Receptor Protein-Tyrosine Kinases

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.

Alternate JournalJ. Cell Biol.
PubMed ID22665521
PubMed Central IDPMC3373410
Grant ListI01 BX001017 / BX / BLRD VA / United States
R01 GM081336 / GM / NIGMS NIH HHS / United States
R01-GM081336 / GM / NIGMS NIH HHS / United States
U54-CA112967 / CA / NCI NIH HHS / United States