Epidermal growth factor-induced enhancement of glioblastoma cell migration in 3D arises from an intrinsic increase in speed but an extrinsic matrix- and proteolysis-dependent increase in persistence.

TitleEpidermal growth factor-induced enhancement of glioblastoma cell migration in 3D arises from an intrinsic increase in speed but an extrinsic matrix- and proteolysis-dependent increase in persistence.
Publication TypeJournal Article
Year of Publication2008
AuthorsKim, H-D, Guo, TW, Wu, AP, Wells, A, Gertler, FB, Lauffenburger, DA
JournalMol Biol Cell
Volume19
Issue10
Pagination4249-59
Date Published2008 Oct
ISSN1939-4586
KeywordsBrain Neoplasms, Cell Line, Tumor, Cell Membrane, Cell Movement, Collagen, Epidermal Growth Factor, Glioblastoma, Green Fluorescent Proteins, Humans, Ligands, Matrix Metalloproteinase 14, Models, Biological, Peptide Hydrolases, rac1 GTP-Binding Protein, Time Factors
Abstract

Epidermal growth factor (EGF) receptor-mediated cell migration plays a vital role in invasion of many tumor types. EGF receptor ligands increase invasiveness in vivo, but it remains unclear how consequent effects on intrinsic cell motility behavior versus effects on extrinsic matrix properties integrate to result in net increase of translational speed and/or directional persistence of migration in a 3D environment. Understanding this convolution is important for therapeutic targeting of tumor invasion, as key regulatory pathways for intrinsic versus extrinsic effects may not be coincident. Accordingly, we have undertaken a quantitative single-cell imaging study of glioblastoma cell movement in 3D matrices and on 2D substrata across a range of collagen densities with systematic variation of protease-mediated matrix degradation. In 3D, EGF induced a mild increase in cell speed and a strong increase in directional persistence, the latter depending heavily on matrix density and EGF-stimulated protease activity. In contrast, in 2D, EGF induced a similarly mild increase in speed but conversely a decrease in directional persistence (both independent of protease activity). Thus, the EGF-enhanced 3D tumor cell migration results only partially from cell-intrinsic effects, with override of cell-intrinsic persistence decrease by protease-mediated cell-extrinsic reduction of matrix steric hindrance.

DOI10.1091/mbc.E08-05-0501
Alternate JournalMol. Biol. Cell
PubMed ID18632979
PubMed Central IDPMC2555959
Grant ListI01 BX001017 / BX / BLRD VA / United States
U54-CA112967 / CA / NCI NIH HHS / United States
U54-GM064346 / GM / NIGMS NIH HHS / United States