Dataset Information

Glioma expansion in collagen I matrices: analyzing collagen concentration-dependent growth and motility patterns.

ABSTRACT: We study the growth and invasion of glioblastoma multiforme (GBM) in three-dimensional collagen I matrices of varying collagen concentration. Phase-contrast microscopy studies of the entire GBM system show that invasiveness at early times is limited by available collagen fibers. At early times, high collagen concentration correlates with more effective invasion. Conversely, high collagen concentration correlates with inhibition in the growth of the central portion of GBM, the multicellular tumor spheroid. Analysis of confocal reflectance images of the collagen matrices quantifies how the collagen matrices differ as a function of concentration. Studying invasion on the length scale of individual invading cells with a combination of confocal and coherent anti-Stokes Raman scattering microscopy reveals that the invasive GBM cells rely heavily on cell-matrix interactions during invasion and remodeling.

SUBMITTER: Kaufman LJ

PROVIDER: S-EPMC1366562 | biostudies-literature | 2005 Jul

REPOSITORIES: biostudies-literature

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Glioma expansion in collagen I matrices: analyzing collagen concentration-dependent growth and motility patterns.

Kaufman L J LJ Brangwynne C P CP Kasza K E KE Filippidi E E Gordon V D VD Deisboeck T S TS Weitz D A DA

Biophysical journal 20050422 1

We study the growth and invasion of glioblastoma multiforme (GBM) in three-dimensional collagen I matrices of varying collagen concentration. Phase-contrast microscopy studies of the entire GBM system show that invasiveness at early times is limited by available collagen fibers. At early times, high collagen concentration correlates with more effective invasion. Conversely, high collagen concentration correlates with inhibition in the growth of the central portion of GBM, the multicellular tumor ...[more]

PMID: 15849239

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Project description:Previous studies have shown that platelet derived growth factor (PDGF) can stimulate corneal keratocyte spreading and migration within 3-D collagen matrices, without inducing transformation to a contractile, fibroblastic phenotype. The goal of this study was to investigate the role of matrix metalloproteinases (MMPs) in regulating PDGF-induced changes in keratocyte motility and mechanical differentiation. Rabbit corneal keratocytes were isolated and cultured in serum-free media (S-) to maintain their quiescent phenotype. A nested collagen matrix construct was used to assess 3-D cell migration, and a standard collagen matrix model was used to assess cell morphology and cell-mediated matrix contraction. In both cases constructs were cultured in S- supplemented with PDGF, with or without the broad spectrum MMP inhibitors GM6001 or BB-94. After 4 days, f-actin, nuclei and collagen fibrils were imaged using confocal microscopy. To assess sub-cellular mechanical activity (extension and retraction of cell processes), time-lapse DIC imaging was also performed. MT1-MMP expression and MMP-mediated collagen degradation were also examined. Results demonstrated that neither GM6001 nor BB-94 affected corneal keratocyte viability or proliferation in 3-D culture. PDGF stimulated elongation and migration of corneal keratocytes within type I collagen matrices, without causing a loss of their dendritic morphology or inducing formation of intracellular stress fibers. Treatment with GM6001 and BB-94 inhibited PDGF-induced keratocyte spreading and migration. Relatively low levels of keratocyte-induced matrix contraction were also maintained in PDGF, and the amount of PDGF-induced collagen degradation was similar to that observed in S- controls. The collagen degradation pattern was consistent with membrane-associated MMP activity, and keratocytes showed positive staining for MT1-MMP, albeit weak. Both matrix contraction and collagen degradation were reduced by MMP inhibition. For most outcome measures, the inhibitory effect of BB-94 was significantly greater than that of GM6001. Overall, the data demonstrate for the first time that even under conditions in which low levels of contractility and extracellular matrix proteolysis are maintained, MMPs still play an important role in mediating cell spreading and migration within 3-D collagen matrices. This appears to be mediated at least in part by membrane-tethered MMPs, such as MT1-MMP.

Dataset Information

Glioma expansion in collagen I matrices: analyzing collagen concentration-dependent growth and motility patterns.

Publications

Glioma expansion in collagen I matrices: analyzing collagen concentration-dependent growth and motility patterns.

Similar Datasets

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