title: Microvesicles released from tumor cells disrupt epithelial cell morphology and contractility.
abstract: During tumor progression, cancer cells interact and communicate with non-malignant cells within their local microenvironment. Microvesicles (MV) derived from human cancer cells play an important role in mediating this communication. Another critical aspect of cancer progression involves widespread ECM remodeling, which occur both at the primary and metastatic sites. ECM remodeling and reorganization within the tumor microenvironment is generally attributed to fibroblasts. Here, using MCF10a cells, a well-characterized breast epithelial cell line that exhibits a non-malignant epithelial phenotype, and MVs shed by aggressive MDA-MB-231 carcinoma cells, we show that non-malignant epithelial cells can participate in ECM reorganization of 3D collagen matrices following their treatment with cancer cell-derived MVs. In addition, MVs trigger several changes in epithelial cells under 3D culture conditions. Furthermore, we show that this ECM reorganization is associated with an increase in cellular traction force following MV treatment, higher acto-myosin contractility, and higher FAK activity. Overall, our findings suggest that MVs derived from tumor cells can contribute to ECM reorganization occurring within the tumor microenvironment by enhancing the contractility of non-malignant epithelial cells.
authors.affiliation: Department of Biomedical Engineering, Cornell University, Ithaca, NY 14853, United States.
authors.forename: Francois
authors.initials: F
authors.lastname: Bordeleau
authors.affiliation: Department of Biomedical Engineering, Cornell University, Ithaca, NY 14853, United States.
authors.forename: Bryan
authors.initials: B
authors.lastname: Chan
authors.affiliation: Department of Biomedical Sciences, Cornell University, Ithaca, NY 14853, United States.
authors.forename: Marc A
authors.initials: MA
authors.lastname: Antonyak
authors.affiliation: Department of Biomedical Engineering, Cornell University, Ithaca, NY 14853, United States.
authors.forename: Marsha C
authors.initials: MC
authors.lastname: Lampi
authors.affiliation: Department of Biomedical Sciences, Cornell University, Ithaca, NY 14853, United States; Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, United States.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Cerione
authors.affiliation: Department of Biomedical Engineering, Cornell University, Ithaca, NY 14853, United States. Electronic address: cak57@cornell.edu.
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Reinhart-King
mesh_terms: D002460:Cell Line; D045744:Cell Line, Tumor; D055252:Cell-Derived Microparticles / Q000502:physiology*; D003094:Collagen / Q000502:physiology; D004847:Epithelial Cells / Q000502:physiology*; D005109:Extracellular Matrix / Q000502:physiology*; D006801:Humans; D059016:Tumor Microenvironment / Q000502:physiology*
chemical_list: D003094:Collagen
keywords: Cell contractility; Extracellular matrix; Microvesicle; Oncosomes; Tumor microenvironment