Enhanced Invasion of Metastatic Cancer Cells via Extracellular Matrix Interface
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{"title"=>"Enhanced invasion of metastatic cancer cells via extracellular matrix interface", "type"=>"journal", "authors"=>[{"first_name"=>"Jiangrui", "last_name"=>"Zhu", "scopus_author_id"=>"56525468400"}, {"first_name"=>"Long", "last_name"=>"Liang", "scopus_author_id"=>"56395941100"}, {"first_name"=>"Yang", "last_name"=>"Jiao", "scopus_author_id"=>"21834011800"}, {"first_name"=>"Liyu", "last_name"=>"Liu", "scopus_author_id"=>"57053861000"}], "year"=>2015, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"25706718", "doi"=>"10.1371/journal.pone.0118058", "sgr"=>"84923321140", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "scopus"=>"2-s2.0-84923321140", "issn"=>"19326203", "pui"=>"602475473"}, "id"=>"e0a8c1bc-acdb-341f-8562-23ca7a203788", "abstract"=>"Cancer cell invasion is a major component of metastasis and is responsible for extensive cell diffusion into and major destruction of tissues. Cells exhibit complex invasion modes, including a variety of collective behaviors. This phenomenon results in the structural heterogeneity of the extracellular matrix (ECM) in tissues. Here, we systematically investigated the environmental heterogeneity facilitating tumor cell invasion via a combination of in vitro cell migration experiments and computer simulations. Specifically, we constructed an ECM microenvironment in a microfabricated biochip and successfully created a three-dimensional (3D) funnel-like matrigel interface inside. Scanning electron microscopy demonstrated that the interface was at the interior defects of the nano-scale molecular anisotropic orientation and the localized structural density variations in the matrigel. Our results, particularly the correlation of the collective migration pattern with the geometric features of the funnel-like interface, indicate that this heterogeneous in vitro ECM structure strongly guides and promotes aggressive cell invasion in the rigid matrigel space. A cellular automaton model was proposed based on our experimental observations, and the associated quantitative analysis indicated that cell invasion was initiated and controlled by several mechanisms, including microenvironment heterogeneity, long-range cell-cell homotype and gradient-driven directional cellular migration. Our work shows the feasibility of constructing a complex and heterogeneous in vitro 3D ECM microenvironment that mimics the in vivo environment. Moreover, our results indicate that ECM heterogeneity is essential in controlling collective cell invasive behaviors and therefore determining metastasis efficiency.", "link"=>"http://www.mendeley.com/research/enhanced-invasion-metastatic-cancer-cells-via-extracellular-matrix-interface-1", "reader_count"=>41, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Researcher"=>5, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>14, "Student > Master"=>8, "Student > Bachelor"=>6, "Professor"=>1, "Other"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Researcher"=>5, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>14, "Student > Master"=>8, "Student > Bachelor"=>6, "Professor"=>1, "Other"=>1}, "reader_count_by_subject_area"=>{"Engineering"=>7, "Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>5, "Materials Science"=>2, "Medicine and Dentistry"=>2, "Agricultural and Biological Sciences"=>16, "Arts and Humanities"=>1, "Physics and Astronomy"=>3, "Chemical Engineering"=>1, "Computer Science"=>2, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>7}, "Materials Science"=>{"Materials Science"=>2}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Physics and Astronomy"=>{"Physics and Astronomy"=>3}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>16}, "Computer Science"=>{"Computer Science"=>2}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>5}, "Unspecified"=>{"Unspecified"=>1}, "Chemical Engineering"=>{"Chemical Engineering"=>1}, "Arts and Humanities"=>{"Arts and Humanities"=>1}}, "reader_count_by_country"=>{"France"=>2}, "group_count"=>1}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1921408"], "description"=>"<p>Snapshots of the simulated collective migration pattern corresponding to the three stages in the experimental observations.</p>", "links"=>[], "tags"=>["scanning electron microscopy", "heterogeneity", "cell invasion", "matrigel", "3 D ECM microenvironment", "Extracellular Matrix Interface Cancer cell invasion", "tumor cell invasion", "cell migration experiments", "interface", "metastatic cancer cells"], "article_id"=>1315902, "categories"=>["Biological Sciences"], "users"=>["Jiangrui Zhu", "Long Liang", "Yang Jiao", "Liyu Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0118058.g007", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Snapshots_of_the_simulated_collective_migration_pattern_corresponding_to_the_three_stages_in_the_experimental_observations_/1315902", "title"=>"Snapshots of the simulated collective migration pattern corresponding to the three stages in the experimental observations.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-02-23 04:01:28"}
  • {"files"=>["https://ndownloader.figshare.com/files/1921405"], "description"=>"<p>(A-C) Cartoons explaining the different phases of collective cell invasion. (D) shows that the MDA-MB-231 cells sensed the interface and began invading the matrigel at 48 hours; (B) The MDA-MB-231 cells’ invasive branches increased following the matrigel interface at 96 hours. Some branches link and form a network, as indicated by the red circle. (C) After the partial interface was filled with the cells, the frontier cells escaped from the interface confinement and produced finger-like invasions in the homogenous matrigel, confirming the strong invasion of the MDA-MB-231 cells in heterogeneous gel space.</p>", "links"=>[], "tags"=>["scanning electron microscopy", "heterogeneity", "cell invasion", "matrigel", "3 D ECM microenvironment", "Extracellular Matrix Interface Cancer cell invasion", "tumor cell invasion", "cell migration experiments", "interface", "metastatic cancer cells"], "article_id"=>1315899, "categories"=>["Biological Sciences"], "users"=>["Jiangrui Zhu", "Long Liang", "Yang Jiao", "Liyu Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0118058.g005", "stats"=>{"downloads"=>0, "page_views"=>23, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_MDA_MB_231_collective_cell_invasion_in_the_matrigel_with_3D_interface_/1315899", "title"=>"MDA-MB-231 collective cell invasion in the matrigel with 3D interface.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-02-23 04:01:28"}
  • {"files"=>["https://ndownloader.figshare.com/files/1921404"], "description"=>"<p>(A) Cartoon showing that the heterogeneous matrigel is composed of matrigel I (red) and matrigel II (blue). The two sections form a funnel-like 3D interface. (B) The upper inset shows the matrigel gel structure preparation. After matrigel I in the channel gelled for 30 min, the chip was tilted 30°-45°. The matrigel I formed a funnel structure due to gravity and gel adhesion. Then, matrigel II was injected into the cavity. The lower inset shows the interface from the side view. (C) The red arrows indicate the gel interface in the experiment.</p>", "links"=>[], "tags"=>["scanning electron microscopy", "heterogeneity", "cell invasion", "matrigel", "3 D ECM microenvironment", "Extracellular Matrix Interface Cancer cell invasion", "tumor cell invasion", "cell migration experiments", "interface", "metastatic cancer cells"], "article_id"=>1315898, "categories"=>["Biological Sciences"], "users"=>["Jiangrui Zhu", "Long Liang", "Yang Jiao", "Liyu Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0118058.g004", "stats"=>{"downloads"=>0, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Formation_of_the_matrigel_interface_/1315898", "title"=>"Formation of the matrigel interface.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-02-23 04:01:28"}
  • {"files"=>["https://ndownloader.figshare.com/files/1921399"], "description"=>"<p>The interface has a horizontal molecular orientation and reduced localized density that produced defects inside the gel.</p>", "links"=>[], "tags"=>["scanning electron microscopy", "heterogeneity", "cell invasion", "matrigel", "3 D ECM microenvironment", "Extracellular Matrix Interface Cancer cell invasion", "tumor cell invasion", "cell migration experiments", "interface", "metastatic cancer cells"], "article_id"=>1315893, "categories"=>["Biological Sciences"], "users"=>["Jiangrui Zhu", "Long Liang", "Yang Jiao", "Liyu Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0118058.g001", "stats"=>{"downloads"=>5, "page_views"=>329, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_SEM_image_of_the_interface_between_the_matrigel_I_and_matrigel_II_sections_/1315893", "title"=>"SEM image of the interface between the matrigel I and matrigel II sections.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-02-23 04:01:28"}
  • {"files"=>["https://ndownloader.figshare.com/files/1921407"], "description"=>"<p>Right panel: associated Voronoi tessellation of the plane into polygons.</p>", "links"=>[], "tags"=>["scanning electron microscopy", "heterogeneity", "cell invasion", "matrigel", "3 D ECM microenvironment", "Extracellular Matrix Interface Cancer cell invasion", "tumor cell invasion", "cell migration experiments", "interface", "metastatic cancer cells"], "article_id"=>1315901, "categories"=>["Biological Sciences"], "users"=>["Jiangrui Zhu", "Long Liang", "Yang Jiao", "Liyu Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0118058.g006", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Left_panel_packing_of_hard_disks_generated_by_random_sequential_addition_/1315901", "title"=>"Left panel: packing of hard disks generated by random sequential addition.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-02-23 04:01:28"}
  • {"files"=>["https://ndownloader.figshare.com/files/1921401"], "description"=>"<p>(A) Diagram sketch of the PDMS chip. The horizontal cylinder channel between the two chambers is filled with matrigel (red). The left chamber is filled with the medium with 1.0% FBS, whereas the right chamber is filled with the medium with 10.0% FBS. (B) The medium with 10.0% FBS and 1.0% FBS established an FBS gradient along the sandwiched matrigel. (C) Fluorescent image of the matrigel zone. The blue line indicates the matrigel. The left side with the lower gray value on shows the RPMI 1640 medium without dextran-rhodamine, and the right zone with the larger gray value represents the RPMI 1640 medium with dextran-rhodamine. The matrigel zone has a gradually decreasing gray color, indicating the establishment of a dextran-rhodamine gradient. (D) Quantitative analysis of the dextran-rhodamine gradient in the time- and space-dependent establishment in the matrigel. The gradient was established in 3 hours and remained stable after 9–48 hours.</p>", "links"=>[], "tags"=>["scanning electron microscopy", "heterogeneity", "cell invasion", "matrigel", "3 D ECM microenvironment", "Extracellular Matrix Interface Cancer cell invasion", "tumor cell invasion", "cell migration experiments", "interface", "metastatic cancer cells"], "article_id"=>1315895, "categories"=>["Biological Sciences"], "users"=>["Jiangrui Zhu", "Long Liang", "Yang Jiao", "Liyu Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0118058.g002", "stats"=>{"downloads"=>0, "page_views"=>20, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Microfluidic_device_and_its_gradient_establishment_in_the_matrigel_/1315895", "title"=>"Microfluidic device and its gradient establishment in the matrigel.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-02-23 04:01:28"}
  • {"files"=>["https://ndownloader.figshare.com/files/1921402"], "description"=>"<p>(A) The MDA-MB-231 cells attached to the matrigel side surface wall at 0 hours. The red line shows the front of the cell group. (B) MDA-MB-231 cell invasion in the matrigel at 96 hours. The cells and matrigel digestion caused gel shrinkage compared with the cell front at 0 hours. (C) Few cells in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0118058#pone.0118058.g003\" target=\"_blank\">Fig. 3B</a> stretched out and exhibited slight invasion into the matrigel, as the white arrows denote, indicating that MDA-MB-231 cells could not invade into the stiff matrigel of 100% concentration.</p>", "links"=>[], "tags"=>["scanning electron microscopy", "heterogeneity", "cell invasion", "matrigel", "3 D ECM microenvironment", "Extracellular Matrix Interface Cancer cell invasion", "tumor cell invasion", "cell migration experiments", "interface", "metastatic cancer cells"], "article_id"=>1315896, "categories"=>["Biological Sciences"], "users"=>["Jiangrui Zhu", "Long Liang", "Yang Jiao", "Liyu Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0118058.g003", "stats"=>{"downloads"=>1, "page_views"=>29, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_MDA_MB_231_cell_invasion_in_the_structurally_homogeneous_matrigel_/1315896", "title"=>"MDA-MB-231 cell invasion in the structurally homogeneous matrigel.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-02-23 04:01:28"}
  • {"files"=>["https://ndownloader.figshare.com/files/1921409"], "description"=>"<p>The parameters values are also provided whenever possible, depending on the specified parameter values and the positions of the cells, and generally vary during the simulation.</p><p>Summary of the simulation parameters.</p>", "links"=>[], "tags"=>["scanning electron microscopy", "heterogeneity", "cell invasion", "matrigel", "3 D ECM microenvironment", "Extracellular Matrix Interface Cancer cell invasion", "tumor cell invasion", "cell migration experiments", "interface", "metastatic cancer cells"], "article_id"=>1315903, "categories"=>["Biological Sciences"], "users"=>["Jiangrui Zhu", "Long Liang", "Yang Jiao", "Liyu Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0118058.t001", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Summary_of_the_simulation_parameters_/1315903", "title"=>"Summary of the simulation parameters.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-02-23 04:01:28"}

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{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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