Opposing Roles for CD34 in B16 Melanoma Tumor Growth Alter Early Stage Vasculature and Late Stage Immune Cell Infiltration
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{"title"=>"Opposing roles for CD34 in B16 melanoma tumor growth alter early stage vasculature and late stage immune cell infiltration", "type"=>"journal", "authors"=>[{"first_name"=>"Steven", "last_name"=>"Maltby", "scopus_author_id"=>"6507446799"}, {"first_name"=>"Spencer", "last_name"=>"Freeman", "scopus_author_id"=>"23110456700"}, {"first_name"=>"Matthew J.", "last_name"=>"Gold", "scopus_author_id"=>"7402444023"}, {"first_name"=>"Jennifer H E", "last_name"=>"Baker", "scopus_author_id"=>"8149582200"}, {"first_name"=>"Andrew I.", "last_name"=>"Minchinton", "scopus_author_id"=>"7004703879"}, {"first_name"=>"Michael R.", "last_name"=>"Gold", "scopus_author_id"=>"8789395400"}, {"first_name"=>"Calvin D.", "last_name"=>"Roskelley", "scopus_author_id"=>"7004526388"}, {"first_name"=>"Kelly M.", "last_name"=>"McNagny", "scopus_author_id"=>"6701876377"}], "year"=>2011, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"361607782", "doi"=>"10.1371/journal.pone.0018160", "pmid"=>"21494591", "issn"=>"19326203", "sgr"=>"79954547294", "scopus"=>"2-s2.0-79954547294", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)"}, "id"=>"96c04143-020c-3e69-9749-397f053b3c21", "abstract"=>"Tumor growth and metastasis are determined by the complex interplay of factors, including those intrinsic to tumor cells and extrinsic factors associated with the tumor microenvironment. Our previous work demonstrated key roles for CD34 in the maintenance of vascular integrity and eosinophil and mast cell homing. Since both of these functions affect tumor development, we characterized the effect of CD34 ablation on tumor growth using the B16F1 melanoma model. Intriguingly, we found that CD34 plays a biphasic role in tumor progression. In early growth, both subcutaneous-injected tumors and intravenous-injected lung metastases grew more slowly in Cd34(-/-) mice. This correlated with abnormal vessel morphology and increased vascular permeability in these mice. Bone marrow transplantation experiments confirmed that this reflects a non-hematopoietic function of CD34. At later stages, subcutaneous tumor growth was accelerated in Cd34(-/-) mice and surpassed growth in wildtype mice. Bone marrow chimera experiments demonstrated this difference was due to a hematopoietic function for CD34 and, correspondingly we found reduced intra-tumor mast cell numbers in Cd34(-/-) mice. In aggregate, our analysis reveals a novel role for CD34 in both early and late tumor growth and provides novel insights into the role of the tumor microenvironment in tumor progression.", "link"=>"http://www.mendeley.com/research/opposing-roles-cd34-b16-melanoma-tumor-growth-alter-early-stage-vasculature-late-stage-immune-cell-i", "reader_count"=>24, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>4, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>16, "Student > Bachelor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>4, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>16, "Student > Bachelor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Engineering"=>1, "Biochemistry, Genetics and Molecular Biology"=>3, "Agricultural and Biological Sciences"=>12, "Medicine and Dentistry"=>5, "Immunology and Microbiology"=>2}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>5}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>12}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"Republic of Singapore"=>1, "Canada"=>1, "Chile"=>1}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/784817"], "description"=>"<p>A, CMFDA-labeled B16F1 cells (green) were coinjected <i>i.v.</i> with fluorescent dextran (red) and lungs were removed after 4 hours, fixed, sectioned and imaged. Representative sections are shown. Tumor cells were quantified as extravasated (green – solid arrows), or within the microvasculature (yellow – hollow arrows). Scale bar, 50 µm, inset = 2×zoom. B, Proportion (%) of tumor cells extravasated per section (n = 5 lungs per genotype, >5 sections per lung, *represents p<0.05; Error bars = SEM).</p>", "links"=>[], "tags"=>["extravasation"], "article_id"=>455184, "categories"=>["Developmental Biology", "Immunology"], "users"=>["Steven Maltby", "Spencer Freeman", "Matthew J. Gold", "Jennifer H. E. Baker", "Andrew I. Minchinton", "Michael R. Gold", "Calvin D. Roskelley", "Kelly M. McNagny"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0018160.g004", "stats"=>{"downloads"=>2, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Increased_tumor_cell_extravasation_in_Cd34_8722_8722_animals_/455184", "title"=>"Increased tumor cell extravasation in <i>Cd34<sup>−/−</sup></i> animals.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 19:18:33"}
  • {"files"=>["https://ndownloader.figshare.com/files/785105"], "description"=>"<p>Model schematic of CD34 function in the tumor microenvironment, highlighting effects on vascular integrity, associated with decreased tumor growth at an early time-point (day 14) and immune cell accumulation, associated with increased tumor growth at a later time-point (day 19) in <i>Cd34<sup>−/−</sup></i> mice.</p>", "links"=>[], "tags"=>["immunology", "dermatology"], "article_id"=>455473, "categories"=>["Developmental Biology", "Immunology"], "users"=>["Steven Maltby", "Spencer Freeman", "Matthew J. Gold", "Jennifer H. E. Baker", "Andrew I. Minchinton", "Michael R. Gold", "Calvin D. Roskelley", "Kelly M. McNagny"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0018160.g007", "stats"=>{"downloads"=>1, "page_views"=>48, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_CD34_function_in_the_tumor_microenvironment_/455473", "title"=>"CD34 function in the tumor microenvironment.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 19:20:12"}
  • {"files"=>["https://ndownloader.figshare.com/files/784702"], "description"=>"<p>Carbocyanine fluorescence intensity quantified A, proximal to CD31<sup>+</sup> vessels (at distance 0 µm) and B, with increasing distance from the nearest vessel (CD31<sup>+</sup>), in day 14 tumors. C, Average distance of each pixel within the tumor tissue from the nearest CD31<sup>+</sup> staining pixel. D, Perfused vessels (%), corresponding to the percentage of CD31<sup>+</sup> pixels colocalized with carbocyanine staining. For carbocyanine data, one outlier per genotype was removed prior to analysis. (n = 5 for carbocyanine, n = 6 for average distance, *represents p<0.05; **represents p<0.01; Error bars = SEM). Representative CT images of tumors excised 14 days post-injection and perfused with Microfil contrast reagent from E, <i>Cd34<sup>+/+</sup></i> and F, <i>Cd34<sup>−/−</sup></i> mice. Scale bars, 2 mm (n = 3).</p>", "links"=>[], "tags"=>["carbocyanine", "leakage", "altered", "morphology", "subcutaneously-injected", "tumors"], "article_id"=>455058, "categories"=>["Developmental Biology", "Immunology"], "users"=>["Steven Maltby", "Spencer Freeman", "Matthew J. Gold", "Jennifer H. E. Baker", "Andrew I. Minchinton", "Michael R. Gold", "Calvin D. Roskelley", "Kelly M. McNagny"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0018160.g003", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Increased_carbocyanine_leakage_and_altered_vessel_morphology_in_subcutaneously_injected_tumors_from_Cd34_8722_8722_animals_/455058", "title"=>"Increased carbocyanine leakage and altered vessel morphology in subcutaneously-injected tumors from <i>Cd34<sup>−/−</sup></i> animals.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 19:17:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/784983"], "description"=>"<p>Toluidine blue staining of A, peri-tumoral mast cells in tissues surrounding tumors and B, intra-tumoral mast cells within tumor tissues. (arrows, mast cells; dotted line, tumor boundary). Mast cell counts in <i>s.c.-</i>injected tumors from <i>Cd34<sup>+/+</sup></i> and <i>Cd34<sup>−/−</sup></i> animals at C, day 14 (pooled from three experiments, <i>Cd34<sup>+/+</sup></i> n = 13, <i>Cd34<sup>−/−</sup></i> n = 16) and D, day 19 (pooled from three experiments, n = 13). Counts in tumors from E, <i>Cd34<sup>+/+</sup></i> or <i>Cd34<sup>−/−</sup></i> animals reconstituted with wildtype Ly5.1 marrow at day 14 (pooled from three experiments, Ly5.1 into <i>Cd34<sup>+/+</sup></i> n = 13, Ly5.1 into <i>Cd34<sup>−/−</sup></i> n = 14) and F, in wildtype Ly5.1 animals reconstituted with either <i>Cd34<sup>+/+</sup></i> or <i>Cd34<sup>−/−</sup></i> bone marrow at day 19 (pooled from three experiments, <i>Cd34<sup>+/+</sup></i> into Ly5.1 n = 11, <i>Cd34<sup>−/−</sup></i> into Ly5.1 n = 13). (*represents p<0.05; Error bars = SEM).</p>", "links"=>[], "tags"=>["infiltration", "reduced"], "article_id"=>455347, "categories"=>["Developmental Biology", "Immunology"], "users"=>["Steven Maltby", "Spencer Freeman", "Matthew J. Gold", "Jennifer H. E. Baker", "Andrew I. Minchinton", "Michael R. Gold", "Calvin D. Roskelley", "Kelly M. McNagny"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0018160.g006", "stats"=>{"downloads"=>1, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Mast_cell_tumor_infiltration_is_reduced_in_Cd34_8722_8722_mice_/455347", "title"=>"Mast cell tumor infiltration is reduced in <i>Cd34<sup>−/−</sup></i> mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 19:19:30"}
  • {"files"=>["https://ndownloader.figshare.com/files/784358"], "description"=>"<p>A, Average tumor mass 14 days after subcutaneous injection of 5×10<sup>5</sup> B16F1-OVA cells. (Pooled from three experiments, <i>Cd34<sup>+/+</sup></i> n = 12; <i>Cd34<sup>−/−</sup></i> n = 15). B, Average number of lung metastases 12 days after intravenous injection of 3×10<sup>5</sup> B16F1-OVA cells. (<i>Cd34<sup>+/+</sup></i> n = 5, <i>Cd34<sup>−/−</sup></i> n = 6, *represents p<0.05; Error bars = SEM). C, Representative photomicrographs from s.c.-injected tumor sections stained for CD34 and CD31 or carbocyanine fluorescence, as indicated (CD31-red, CD34-blue, carbocyanine-green).</p>", "links"=>[], "tags"=>["reduced", "animals", "cd34"], "article_id"=>454708, "categories"=>["Developmental Biology", "Immunology"], "users"=>["Steven Maltby", "Spencer Freeman", "Matthew J. Gold", "Jennifer H. E. Baker", "Andrew I. Minchinton", "Michael R. Gold", "Calvin D. Roskelley", "Kelly M. McNagny"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0018160.g001", "stats"=>{"downloads"=>0, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Melanoma_growth_is_reduced_in_Cd34_8722_8722_animals_at_day_14_with_CD34_expression_on_vasculature_/454708", "title"=>"Melanoma growth is reduced in <i>Cd34<sup>−/−</sup></i> animals at day 14, with CD34 expression on vasculature.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 19:15:53"}
  • {"files"=>["https://ndownloader.figshare.com/files/784887"], "description"=>"<p>A, Average <i>s.c.-</i>injected tumor masses 19 days post-injection in <i>Cd34<sup>+/+</sup></i> and <i>Cd34<sup>−/−</sup></i> animals. (Pooled from three experiments, <i>Cd34<sup>+/+</sup></i> n = 15, <i>Cd34<sup>−/−</sup></i> n = 16). B, Average tumor mass at day 19 in wildtype Ly5.1 animals reconstituted with either <i>Cd34<sup>+/+</sup></i> or <i>Cd34<sup>−/−</sup></i> bone marrow. (Pooled from two experiments, <i>Cd34<sup>+/+</sup></i> into Ly5.1 n = 11, <i>Cd34<sup>−/−</sup></i> into Ly5.1 n = 13). (*represents p<0.05; Error bars = SEM).</p>", "links"=>[], "tags"=>["surpasses", "hematopoietic"], "article_id"=>455250, "categories"=>["Developmental Biology", "Immunology"], "users"=>["Steven Maltby", "Spencer Freeman", "Matthew J. Gold", "Jennifer H. E. Baker", "Andrew I. Minchinton", "Michael R. Gold", "Calvin D. Roskelley", "Kelly M. McNagny"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0018160.g005", "stats"=>{"downloads"=>1, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Tumor_size_in_Cd34_8722_8722_surpasses_Cd34_by_day_19_due_to_hematopoietic_loss_of_CD34_/455250", "title"=>"Tumor size in <i>Cd34<sup>−/−</sup></i> surpasses <i>Cd34<sup>+/+</sup></i> by day 19, due to hematopoietic loss of CD34.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 19:18:55"}
  • {"files"=>["https://ndownloader.figshare.com/files/784553"], "description"=>"<p>A, Average tumor mass and B, volume at day 14 in <i>Cd34<sup>+/+</sup></i> or <i>Cd34<sup>−/−</sup></i> animals reconstituted with wildtype Ly5.1 bone marrow. (Pooled from two experiments, <i>Cd34<sup>+/+</sup></i> n = 13, <i>Cd34<sup>−/−</sup></i> n = 14). C, Average tumor mass at day 14, in reciprocal reconstitutions of wildtype Ly5.1 animals with <i>Cd34<sup>+/+</sup></i> or <i>Cd34<sup>−/−</sup></i> bone marrow (n = 9, *represents p<0.05; Error bars = SEM).</p>", "links"=>[], "tags"=>["subcutaneous", "14", "correlates", "cd34", "non-hematopoietic"], "article_id"=>454910, "categories"=>["Developmental Biology", "Immunology"], "users"=>["Steven Maltby", "Spencer Freeman", "Matthew J. Gold", "Jennifer H. E. Baker", "Andrew I. Minchinton", "Michael R. Gold", "Calvin D. Roskelley", "Kelly M. McNagny"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0018160.g002", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Reduced_subcutaneous_tumor_size_at_day_14_correlates_with_loss_of_CD34_on_non_hematopoietic_cells_/454910", "title"=>"Reduced subcutaneous tumor size at day 14 correlates with loss of CD34 on non-hematopoietic cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 19:17:00"}

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