Dimensional control of cancer cell migration.

摘要: Cell migration is a fundamental cellular function that underlies numerous diverse biological processes, including tissue patterning, morphogenesis, immune response, and cancer metastasis. While earlier studies emphasized the importance of chemical factors in cell migration, accumulating evidence suggests physical cues microenvironment also influence motility, local stiffness microstructure extracellular matrix (ECM). Much what we know about molecular mechanisms locomotion stems from in vitro using two-dimensional, ECM-coated surfaces (1). However, wide range cells, such as fibroblasts connective tissues locally invading cells stromal near tumor, migrate three-dimensional even one-dimensional environments. Accumulating dimensionality migratory environment affects motility (2). For instance, features important two-dimensional locomotion, stress fibers focal adhesions, are significantly reduced motile matrix, whereas others critical to nuclear deformation metalloproteinase production, have little or no role (3–8). Cell-derived reconstituted ECM gels been used study migration. Microfabrication techniques employed on lines (3). Although true rarely occur in vivo, assays share certain similarities similar morphology, numbers adhesions relative surfaces. Cells typically in vivo through three-dimensional collagen matrices channels. Three-dimensional longitudinal tracks with bordering interfaces (i.e., channels) formed by large anatomic structures covered by basement membrane, myofibers, fat tissue, perineural, perivascular spaces (9). Similarly, bundled fibrillar interstitial (3,9). Importantly, tumor reported through in vivo. Balzer et al. (10) recently fabricated microfluidic-based device examine chemotactically driven channels different widths. Migration W larger than diameter, dcell) recapitulates hallmarks narrow ≪ mimics physically constricted encountered This showed that, line observations made or assays, dorsoventral polarity, fibers, markedly attenuated confinement (10). Consistent data obtained lines, inhibitors myosin Rho/ROCK did not impair 3-μm (confinement), though these treatments repress Remarkably, metastatic breast persists when F-actin disrupted II inhibited, depends largely microtubule dynamics Microtubule assembly may provide driving force for confined Despite similarities, one-dimensional, three-dimensional, should be considered alike. In this issue Biophysical Journal, Chang (11) demonstrate novel myosin-dependent mechanism “dimensional-sensing” mouse fibroblasts. A migrating traveling rectangular alternating patterned will spend more time results, display fewer smaller well as organized turn generate much lower traction forces underlying surface than cells patterns. The effect inhibition smaller in one dimension two. Constriction critically II-based contractility (11). dimensional sensing mostly lost ras-transformed where ras an oncogene. defect may contribute invasive phenotype transformed defect be due, part, loss regulatory control Ras transformation may reduce decreasing expression. These mimic peeling off primary which essentially at length scales cell, move along suggested intravital microscopy live mouse, i.e., a 2D-to-1D switch dimensions Because organs present scale (9), it would interesting other physiopathologically relevant changes dimensions, i.e., 2D-to-3D 1D-to-3D, determine whether same elucidated play transformation abrogates ability sense changes.