chanically interacting systems of mammary acini. Proc. Natl. Acad. Sci. USA 111, 658-663. http://www.ncbi.nlm.nih.gov/pubmed/24379367. A recent report from ...
Matrix Biology 38 (2014) 1–2
Contents lists available at ScienceDirect
Matrix Biology journal homepage: www.elsevier.com/locate/matbio
Matrix Biology Highlights Tom Neill, Jason Zoeller
© 2014 Published by Elsevier B.V.
1) Collagen lines point toward invasion Reference | Shi, Q., Ghosh, R.P., Engelke, H., Rycroft, C.H., Cassereau, L., Sethian, J.A., Weaver, V.M., Liphardt, J.T., 2014. Rapid disorganization of mechanically interacting systems of mammary acini. Proc. Natl. Acad. Sci. USA 111, 658-663. http://www.ncbi.nlm.nih.gov/pubmed/24379367. A recent report from Shi and colleagues published in PNAS defines tumor cell-collagen interactions via lines as a critical component of the invasive transition1. The authors utilize the 3D-culture mammary acini system to model breast cancer progression. Disruption of established structures and further growth on collagen I resulted in the concentration of collagen around and the formation of collagen lines between groups of acini (Fig. 1). These events were coupled with disorganization of 3D architecture. Compared with acini that did not feature connections, interactions among groups of acini via collagen lines favored the onset, rate and potential to disorganize. The significance of the collagen lines was further evaluated through a series of experiments that sever the line connections. Elimination of the collagen lines completely inhibited the disorganization phenotype as described above. These results highlight interactions between the tumor cells with reciprocal influences on the matrix that promote invasion.
Fig. 1. Collaborative mechanical restructuring of ECM by groups of mammary acini provides feedback for concerted malignant transformation. Pairs or groups of Ras-transformed mammary acini with thinned basement membranes and weakened cell-cell junctions can generate collagen lines which then aid in coordinated and accelerated transition of acinar cells into an invasive phenotype. 20 hours after acini were seeded on collagen gels (field dimension approx. 1mm) the disorganizing acini (red, labeled with H2B-mCherry) are connected mechanically through collagen lines (green, labeled with an EGFP fusion of a collagen binding protein). Overall disorganization of mechanically interacting pairs of acini is more probable, rapid, and extensive than that of a single acinus. The leader cells of disorganizing acini preferentially move along the thick collagen fibers, exhibiting "EMT-like" properties. Figure kindly provided by Shi Q.
http://dx.doi.org/10.1016/j.matbio.2014.09.002 0945-053X/© 2014 Published by Elsevier B.V.
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T. Neill, J. Zoeller / Matrix Biology 38 (2014) 1–2
2) The extracellular matrix and cognitive flexibilities Reference | Happel, M.F., Niekisch, H., Castiblanco-Rivera, L.L., Ohl, F.W., Deliano, M., Frischknecht, R., 2014. Enhanced cognitive flexibility in reversal learning induced by removal of the extracellular matrix in auditory cortex. Proc. Natl. Acad. Sci. USA 111, 2800-2805. http://www.ncbi.nlm.nih.gov/ pubmed/24550310. A recent report from Happel and colleagues published in PNAS provides evidence for brain ECM contributions related to learned behaviors2. The authors deplete ECM via hyaluronidase within the auditory cortex of the Mongolian gerbils and monitored the reverse learning process (Fig. 2). Elimination as such enhanced the animals’ abilities to reverse learn. The cellular basis of the response might however be due to synaptic modulations that would otherwise be blocked via matrix interference.
Fig. 2. Flexible memory re-formation by weakening the brain matrix. The brain’s extracellular matrix mediates structural stability by enwrapping synaptic contacts in the adult brain fundamental for the maintenance of established neuronal networks. Such stability, however, might come with the costs of a lesser degree of freedom when it comes to life-long memory reformations and relearning processes. Adult Mongolian gerbils were trained in a cognitive demanding auditory reversal-learning task in a shuttle-box paradigm. Animals had to discriminate between two sound signals, which were associated with either escaping a foot shock by a compartment change in the test chamber or stay to avoid it. After animals performed the task well, i.e. acquired an established memory of the stimulus contingencies, those were reversed from one day to the other. Local weakening of the structurally rigid ECM by injection of a degrading enzyme within the auditory cortex specifically accelerated the strategy changes required for such reversal learning. Importantly, it neither affected general sensory learning nor erased already established, learned memory traces. Thus, the flexible modulation of the ECM in the mature brain might promote the cognitive flexibility that can build on learned behaviors and allows for an enhanced activity-dependent memory re-formation. Figure kindly provided by Happel MF and Frischknecht R.
