Organized extracellular matrix (ECM), in the form of aligned architectures, is a critical mediator of directed cancer cell migration by contact guidance, leading to metastasis in solid tumors. Current models suggest anisotropic force generation through the engagement of key adhesion and cytoskeletal complexes drives contact-guided migration. Likewise, disrupting the balance between cell–cell and cell–ECM forces, driven by ECM engagement for cells at the tumor–stromal interface, initiates and drives local invasion. Furthermore, processes such as traction forces exerted by cancer and stromal cells, spontaneous reorientation of matrix-producing fibroblasts, and direct binding of ECM modifying proteins lead to the emergence of collagen alignment in tumors. Thus, as we obtain a deeper understanding of the origins of ECM alignment and the mechanisms by which it is maintained to direct invasion, we are poised to use the new paradigm of stroma-targeted therapies to disrupt this vital axis of disease progression in solid tumors.
Bibliographical noteFunding Information:
P.P.P. and this work was supported by Research Scholar Grant, RSG-14-171-01-CSM from the American Cancer Society and the NIH ( U54CA210190 University of Minnesota Physical Sciences in Oncology Center, Project 2 to P.P.P. and R01CA245550 to P.P.P.). A.R. is a Cancer Research Institute Irvington Postdoctoral Fellow supported by the Cancer Research Institute (award number CRI2940 ). The content of this work is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or other funding agencies.
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