title: Comparative mechanisms of cancer cell migration through 3D matrix and physiological microtracks.
abstract: Tumor cell invasion through the stromal extracellular matrix (ECM) is a key feature of cancer metastasis, and understanding the cellular mechanisms of invasive migration is critical to the development of effective diagnostic and therapeutic strategies. Since cancer cell migration is highly adaptable to physiochemical properties of the ECM, it is critical to define these migration mechanisms in a context-specific manner. Although extensive work has characterized cancer cell migration in two- and three-dimensional (3D) matrix environments, the migration program employed by cells to move through native and cell-derived microtracks within the stromal ECM remains unclear. We previously reported the development of an in vitro model of patterned type I collagen microtracks that enable matrix metalloproteinase-independent microtrack migration. Here we show that collagen microtracks closely resemble channel-like gaps in native mammary stroma ECM and examine the extracellular and intracellular mechanisms underlying microtrack migration. Cell-matrix mechanocoupling, while critical for migration through 3D matrix, is not necessary for microtrack migration. Instead, cytoskeletal dynamics, including actin polymerization, cortical tension, and microtubule turnover, enable persistent, polarized migration through physiological microtracks. These results indicate that tumor cells employ context-specific mechanisms to migrate and suggest that selective targeting of cytoskeletal dynamics, but not adhesion, proteolysis, or cell traction forces, may effectively inhibit cancer cell migration through preformed matrix microtracks within the tumor stroma.
authors.affiliation: Department of Biomedical Engineering, Cornell University, Ithaca, New York.
authors.forename: Shawn P
authors.initials: SP
authors.lastname: Carey
authors.affiliation: Department of Biomedical Engineering, Cornell University, Ithaca, New York.
authors.forename: Aniqua
authors.initials: A
authors.lastname: Rahman
authors.affiliation: Department of Biomedical Engineering, Cornell University, Ithaca, New York.
authors.forename: Casey M
authors.initials: CM
authors.lastname: Kraning-Rush
authors.affiliation: Department of Biomedical Engineering, Cornell University, Ithaca, New York.
authors.forename: Bethsabe
authors.initials: B
authors.lastname: Romero
authors.affiliation: Department of Biomedical Engineering, Cornell University, Ithaca, New York.
authors.forename: Sahana
authors.initials: S
authors.lastname: Somasegar
authors.affiliation: Department of Biomedical Engineering, Cornell University, Ithaca, New York.
authors.forename: Olivia M
authors.initials: OM
authors.lastname: Torre
authors.affiliation: Department of Biomedical Engineering, Cornell University, Ithaca, New York.
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Williams
authors.affiliation: Department of Biomedical Engineering, Cornell University, Ithaca, New York cak57@cornell.edu.
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Reinhart-King
mesh_terms: D000199:Actins / Q000378:metabolism; D000205:Actomyosin / Q000378:metabolism; D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D048430:Cell Shape; D003094:Collagen / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D040542:Mechanotransduction, Cellular; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D009361:Neoplasm Invasiveness; D013997:Time Factors; D059016:Tumor Microenvironment
chemical_list: D000199:Actins; D019012:Integrin beta1; D003094:Collagen; D000205:Actomyosin
keywords: microtracks; migration mechanisms; tumor invasion