title: Two-photon laser-generated microtracks in 3D collagen lattices: principles of MMP-dependent and -independent collective cancer cell invasion.
abstract: Cancer invasion into an extracellular matrix (ECM) results from a biophysical reciprocal interplay between the expanding cancer lesion and tissue barriers imposed by the adjacent microenvironment. In vivo, connective tissue provides both densely packed ECM barriers adjacent to channel/track-like spaces and loosely organized zones, both of which may impact cancer invasion mode and efficiency; however little is known about how three-dimensional (3D) spaces and aligned tracks present in interstitial tissue guide cell invasion. We here describe a two-photon laser ablation procedure to generate 3D microtracks in dense 3D collagen matrices that support and guide collective cancer cell invasion. Whereas collective invasion of mammary tumor (MMT) breast cancer cells into randomly organized collagen networks required matrix metalloproteinase (MMP) activity for cell-derived collagen breakdown, re-alignment and track generation, preformed tracks supported MMP-independent collective invasion down to a track caliber of 3 µm. Besides contact guidance along the track of least resistance and initial cell deformation (squeezing), MMP-independent collective cell strands led to secondary track expansion by a pushing mechanism. Thus, two-photon laser ablation is useful to generate barrier-free microtracks in a 3D ECM which guide collective invasion independently of pericellular proteolysis.
authors.affiliation: Microscopical Imaging of the Cell, Department of Cell Biology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Geert Groote Plein 26-28, Nijmegen, HB 6500, The Netherlands.
authors.forename: Olga
authors.initials: O
authors.lastname: Ilina
authors.forename: Gert-Jan
authors.initials: GJ
authors.lastname: Bakker
authors.forename: Angela
authors.initials: A
authors.lastname: Vasaturo
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hofmann
authors.forename: Peter
authors.initials: P
authors.lastname: Friedl
mesh_terms: D000818:Animals; D002465:Cell Movement; D003094:Collagen / Q000378:metabolism*; D005260:Female; D006801:Humans; D007834:Lasers; D015674:Mammary Neoplasms, Animal / Q000378:metabolism / Q000473:pathology*; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D051379:Mice; D055616:Microtechnology; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D018874:Spheroids, Cellular; D054457:Tissue Scaffolds / Q000737:chemistry; D014407:Tumor Cells, Cultured
chemical_list: D003094:Collagen; D020782:Matrix Metalloproteinases