EMT and Acquisition of Stem Cell-Like Properties Are Involved in Spontaneous Formation of Tumorigenic Hybrids between Lung Cancer and Bone Marrow-Derived Mesenchymal Stem Cells
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{"title"=>"EMT and acquisition of stem cell-like properties are involved in spontaneous formation of tumorigenic hybrids between lung cancer and bone marrow-derived mesenchymal stem cells", "type"=>"journal", "authors"=>[{"first_name"=>"Mei Hua", "last_name"=>"Xu", "scopus_author_id"=>"56058210000"}, {"first_name"=>"Xuan", "last_name"=>"Gao", "scopus_author_id"=>"56058205100"}, {"first_name"=>"Dan", "last_name"=>"Luo", "scopus_author_id"=>"7202658357"}, {"first_name"=>"Xiang Dong", "last_name"=>"Zhou", "scopus_author_id"=>"55562246500"}, {"first_name"=>"Wei", "last_name"=>"Xiong", "scopus_author_id"=>"56783168200"}, {"first_name"=>"Guo Xiang", "last_name"=>"Liu", "scopus_author_id"=>"55562087900"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"84895528244", "doi"=>"10.1371/journal.pone.0087893", "pui"=>"372535442", "pmid"=>"24516569", "scopus"=>"2-s2.0-84895528244", "issn"=>"19326203", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)"}, "id"=>"8f415eb1-9856-300a-8b5a-1cb9c18d517c", "abstract"=>"The most deadly phase in cancer progression is metastatic conversion. Epithelial-to-mesenchymal transition (EMT) is a key process by which cancer cells acquire invasive and metastatic phenotypes. In order to spawn macroscopic metastases, disseminated cancer cells would seem to require self-renewal capability. However, the underlying mechanism defining these processes is poorly understood. One possible mechanism underlying metastasis is fusion between myeloid cells and cancer cells. In this study, we found that spontaneously-formed tumorigenic hybrids between bone marrow-derived mesenchymal stem cells (MSCs) and three different non-small cell lung cancer (NSCLC) cell lines contributed to highly malignant subpopulations with both EMT and stem cell-like properties. Hybrids lost their epithelial morphology and assumed a fibroblast-like appearance. Up-regulation of vimentin, α-smooth muscle actin (α-SMA), and fibronectin, and down-regulation of E-cadherin and pancytokeratin were observed in tumorigenic hybrids. These cells also exhibited increased expression of the stem cell marker prominin-1 (CD133) and over-expression of transcription factors OCT4, Nanog, BMI1, Notch1, ALDH1 as well as Sox2, all genes responsible for regulating and maintaining the stem cell phenotype. In addition, in spontaneously-formed tumorigenic hybrids, increased pneumosphere-forming capacity and tumor-forming ability in NOD/SCID mice were detectable. Thus, cell fusion between lung cancer cells and MSCs provides a nonmutational mechanism that could contribute to aberrant gene expression patterns and give rise to highly malignant subpopulations both capable of EMT and with properties of cancer stem cells (CSCs).", "link"=>"http://www.mendeley.com/research/emt-acquisition-stem-celllike-properties-involved-spontaneous-formation-tumorigenic-hybrids-between", "reader_count"=>39, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Researcher"=>4, "Student > Doctoral Student"=>5, "Student > Ph. D. Student"=>11, "Student > Postgraduate"=>1, "Student > Master"=>9, "Other"=>1, "Student > Bachelor"=>3, "Lecturer > Senior Lecturer"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Researcher"=>4, "Student > Doctoral Student"=>5, "Student > Ph. D. Student"=>11, "Student > Postgraduate"=>1, "Student > Master"=>9, "Other"=>1, "Student > Bachelor"=>3, "Lecturer > Senior Lecturer"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Engineering"=>2, "Biochemistry, Genetics and Molecular Biology"=>9, "Agricultural and Biological Sciences"=>12, "Medicine and Dentistry"=>13, "Psychology"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>2}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>13}, "Psychology"=>{"Psychology"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>12}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>9}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"Norway"=>1, "United States"=>1, "Brazil"=>1, "United Kingdom"=>1, "Germany"=>1, "India"=>1}, "group_count"=>3}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1560196"], "description"=>"<p>(<b>A</b>) Soft agar assays: Single cells (1×10<sup>3</sup> per well) were plated into soft agar in 6-well plates in triplicate. Microscopic images and quantification of heterotypic hybrids and respective parental A549, H460 or SK-MES-1 cells. The data are reported as mean ± SEM. (<b>B</b>) Pneumosphere assay: Microscopic images and quantification of heterotypic hybrids and respective parental A549, H460 or SK-MES-1 cells; n = 12. The data are reported as mean ± SEM. Asterisks depict statistically-significant differences between the heterotypic hybrids and respective parental lung cancer cells (*<i>P</i><0.001). Scale bar, 100 µm.</p>", "links"=>[], "tags"=>["developmental biology", "stem cells", "mesenchymal stem cells", "Molecular cell biology", "Cellular types", "oncology", "Basic cancer research", "metastasis", "Cancers and neoplasms", "Lung and intrathoracic tumors", "Cancer risk factors", "heterotypic", "hybrids", "respective", "cancer"], "article_id"=>1079501, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Mei-Hua Xu", "Xuan Gao", "Dan Luo", "Xiang-Dong Zhou", "Wei Xiong", "Guo-Xiang Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087893.g006", "stats"=>{"downloads"=>7, "page_views"=>105, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Tumor_sphere_formation_ability_of_heterotypic_hybrids_and_respective_parental_lung_cancer_cells_/1079501", "title"=>"Tumor sphere formation ability of heterotypic hybrids and respective parental lung cancer cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-06 11:28:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/1560242"], "description"=>"<p>(<b>A</b>) Images, at successive time points, showing reversion of the fibroblastic morphological characteristics of A549/MSC hybrids to an epithelial, A549-like appearance in culture. Scale bars: 500 µm. (<b>B</b>) Immunohistochemical staining for the indicated antigens performed on tumor specimens derived from parental A549 tumor or from tumors generated by subcutaneous injection of A549/MSC hybrids in NOD/SCID mice. Explants of tumor xenografts of A549/MSC hybrids and parental A549 cells displayed similar lung cancer-like morphological characteristics. Scale bar, 100 µm.</p>", "links"=>[], "tags"=>["developmental biology", "stem cells", "mesenchymal stem cells", "Molecular cell biology", "Cellular types", "oncology", "Basic cancer research", "metastasis", "Cancers and neoplasms", "Lung and intrathoracic tumors", "Cancer risk factors", "hybrids", "fibroblast-like", "epithelial", "morphological"], "article_id"=>1079547, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Mei-Hua Xu", "Xuan Gao", "Dan Luo", "Xiang-Dong Zhou", "Wei Xiong", "Guo-Xiang Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087893.g008", "stats"=>{"downloads"=>1, "page_views"=>17, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Reversion_of_A549_MSC_hybrids_from_fibroblast_like_to_epithelial_morphological_characteristics_in_vitro_and_in_vivo_/1079547", "title"=>"Reversion of A549/MSC hybrids from fibroblast-like to epithelial morphological characteristics <i>in</i><i>vitro</i> and <i>in vivo</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-06 11:28:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/1560120"], "description"=>"<p>(<b>A</b>) Fluorescent micrographs of a co-culture of A549-EGFP (green) and MSC-RFP (red), showing formation of double-labeled hybrid cell with two nuclei and a fibroblastic shape (arrows). Scale bar, 50 µm. (<b>B</b>) Fluorescent micrographs, taken at 2-hourly intervals, of co-cultures of SK-MES-1-EGFP (green) with MSC-RFP (red), showing apparent involvement of cell fusion (arrows) and change in color in the interaction of lung cancer cells with MSCs. Scale bar, 10 µm. (<b>C</b>) Quantification of spontaneous hybridization between lung cancer cells (A549-EGFP, H460-EGFP or SK-MES-1-EGFP) and MSC-RFP in high-density co-culture. The number of hybrids was assessed by flow cytometric analysis and expressed as a percentage of the total cells. Data represent the mean ± SEM of three experiments. (<b>D</b>) FISH analysis of HCC827/MSC co-cultures. Male MSCs were cultured with female HCC827 lung cancer cells for 8 days and fixed. FISH (Spectrum red-Y chromosome and Spectrum green-X chromosome) was performed and nuclei were stained with DAPI (blue). Green arrows show X chromosomes and red arrows, Y chromosomes. Male MSCs expressed one Y chromosome and one X chromosome whereas female HCC827 cells expressed only X chromosomes. In HCC827/MSC hybrids: example of two cells, one harboring two nuclei and the other with one nucleus. These two cells each possess a Y chromosome indicating an MSC-derived cell. Scale bar, 25 µm.</p>", "links"=>[], "tags"=>["developmental biology", "stem cells", "mesenchymal stem cells", "Molecular cell biology", "Cellular types", "oncology", "Basic cancer research", "metastasis", "Cancers and neoplasms", "Lung and intrathoracic tumors", "Cancer risk factors", "heterotypic", "hybrids", "cancer", "cells"], "article_id"=>1079436, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Mei-Hua Xu", "Xuan Gao", "Dan Luo", "Xiang-Dong Zhou", "Wei Xiong", "Guo-Xiang Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087893.g001", "stats"=>{"downloads"=>2, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Spontaneous_formation_of_heterotypic_hybrids_between_lung_cancer_cells_and_MSCs_/1079436", "title"=>"Spontaneous formation of heterotypic hybrids between lung cancer cells and MSCs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-06 11:28:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/1560190"], "description"=>"<p>(<b>A</b>) Flow cytometry analysis of CD133 expression in heterotypic hybrids and respective parental lung cancer cells. Percentages of CD133<sup>+</sup> cells are indicated in control antibody and specific antibody-stained cells. Grey and black line indicated negative control and sample, respectively. (<b>B</b>) The expression levels of the mRNAs encoding CD133, Nanog, BMI1, Notch1, ALDH1, Sox2 and OCT4 in spontaneously-formed A549/MSC, H460/MSC and SK-MES-1/MSC heterotypic hybrids relative to respective parental lung cancer cells as determined by QRT-PCR. GAPDH mRNA was used to normalize the variability in template loading. The data are reported as mean ± SEM.</p>", "links"=>[], "tags"=>["developmental biology", "stem cells", "mesenchymal stem cells", "Molecular cell biology", "Cellular types", "oncology", "Basic cancer research", "metastasis", "Cancers and neoplasms", "Lung and intrathoracic tumors", "Cancer risk factors", "stemness", "markers", "heterotypic", "hybrids", "respective", "cancer"], "article_id"=>1079495, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Mei-Hua Xu", "Xuan Gao", "Dan Luo", "Xiang-Dong Zhou", "Wei Xiong", "Guo-Xiang Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087893.g005", "stats"=>{"downloads"=>0, "page_views"=>18, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Expression_of_stemness_markers_in_heterotypic_hybrids_and_respective_parental_lung_cancer_cells_/1079495", "title"=>"Expression of stemness markers in heterotypic hybrids and respective parental lung cancer cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-06 11:28:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/1560281", "https://ndownloader.figshare.com/files/1560282", "https://ndownloader.figshare.com/files/1560283", "https://ndownloader.figshare.com/files/1560284", "https://ndownloader.figshare.com/files/1560287"], "description"=>"<div><p>The most deadly phase in cancer progression is metastatic conversion. Epithelial-to-mesenchymal transition (EMT) is a key process by which cancer cells acquire invasive and metastatic phenotypes. In order to spawn macroscopic metastases, disseminated cancer cells would seem to require self-renewal capability. However, the underlying mechanism defining these processes is poorly understood. One possible mechanism underlying metastasis is fusion between myeloid cells and cancer cells. In this study, we found that spontaneously-formed tumorigenic hybrids between bone marrow-derived mesenchymal stem cells (MSCs) and three different non-small cell lung cancer (NSCLC) cell lines contributed to highly malignant subpopulations with both EMT and stem cell-like properties. Hybrids lost their epithelial morphology and assumed a fibroblast-like appearance. Up-regulation of vimentin, α-smooth muscle actin (α-SMA), and fibronectin, and down-regulation of E-cadherin and pancytokeratin were observed in tumorigenic hybrids. These cells also exhibited increased expression of the stem cell marker prominin-1 (CD133) and over-expression of transcription factors OCT4, Nanog, BMI1, Notch1, ALDH1 as well as Sox2, all genes responsible for regulating and maintaining the stem cell phenotype. In addition, in spontaneously-formed tumorigenic hybrids, increased pneumosphere-forming capacity and tumor-forming ability in NOD/SCID mice were detectable. Thus, cell fusion between lung cancer cells and MSCs provides a nonmutational mechanism that could contribute to aberrant gene expression patterns and give rise to highly malignant subpopulations both capable of EMT and with properties of cancer stem cells (CSCs).</p></div>", "links"=>[], "tags"=>["developmental biology", "stem cells", "mesenchymal stem cells", "Molecular cell biology", "Cellular types", "oncology", "Basic cancer research", "metastasis", "Cancers and neoplasms", "Lung and intrathoracic tumors", "Cancer risk factors", "cell-like", "spontaneous", "tumorigenic", "hybrids", "cancer", "marrow-derived", "mesenchymal"], "article_id"=>1079586, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Mei-Hua Xu", "Xuan Gao", "Dan Luo", "Xiang-Dong Zhou", "Wei Xiong", "Guo-Xiang Liu"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0087893.s001", "https://dx.doi.org/10.1371/journal.pone.0087893.s002", "https://dx.doi.org/10.1371/journal.pone.0087893.s003", "https://dx.doi.org/10.1371/journal.pone.0087893.s004", "https://dx.doi.org/10.1371/journal.pone.0087893.s005"], "stats"=>{"downloads"=>7, "page_views"=>30, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_EMT_and_Acquisition_of_Stem_Cell_Like_Properties_Are_Involved_in_Spontaneous_Formation_of_Tumorigenic_Hybrids_between_Lung_Cancer_and_Bone_Marrow_Derived_Mesenchymal_Stem_Cells_/1079586", "title"=>"EMT and Acquisition of Stem Cell-Like Properties Are Involved in Spontaneous Formation of Tumorigenic Hybrids between Lung Cancer and Bone Marrow-Derived Mesenchymal Stem Cells", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-02-06 11:28:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/1560178"], "description"=>"<p>The migratory and invasive potential of the cells was determined by counting the number of cells that had migrated to the lower surface of the filter in 12 randomly selected microscopic fields per insert. (<b>A</b>) Migration assays: microscopic images and quantification. (<b>B</b>) Invasion assays: microscopy images and quantification. The data are reported as mean ± SEM of three independent experiments. Asterisks depict statistically-significant differences between the heterotypic hybrids and respective parental lung cancer cells (*<i>P</i><0.001). Scale bar, 50 µm.</p>", "links"=>[], "tags"=>["developmental biology", "stem cells", "mesenchymal stem cells", "Molecular cell biology", "Cellular types", "oncology", "Basic cancer research", "metastasis", "Cancers and neoplasms", "Lung and intrathoracic tumors", "Cancer risk factors", "assays", "heterotypic", "hybrids", "respective", "cancer"], "article_id"=>1079483, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Mei-Hua Xu", "Xuan Gao", "Dan Luo", "Xiang-Dong Zhou", "Wei Xiong", "Guo-Xiang Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087893.g004", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Migration_and_invasion_assays_of_heterotypic_hybrids_and_respective_parental_lung_cancer_cells_/1079483", "title"=>"Migration and invasion assays of heterotypic hybrids and respective parental lung cancer cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-06 11:28:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/1560243"], "description"=>"<p>Note: Data are given as number/total (percentage). Control MSCs implanted alone into 10 mice (inoculum, 1×10<sup>6</sup> cells/mouse) were nontumorigenic.</p><p>*Statistically significant difference by two-sided Fisher’s exact test with respect to the rate of tumor incidence by parental lung cancer cells (P<0.001).</p>", "links"=>[], "tags"=>["developmental biology", "stem cells", "mesenchymal stem cells", "Molecular cell biology", "Cellular types", "oncology", "Basic cancer research", "metastasis", "Cancers and neoplasms", "Lung and intrathoracic tumors", "Cancer risk factors", "msc-lung", "carcinoma"], "article_id"=>1079548, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Mei-Hua Xu", "Xuan Gao", "Dan Luo", "Xiang-Dong Zhou", "Wei Xiong", "Guo-Xiang Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087893.t001", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Tumorigenic_Potential_of_MSC_lung_Carcinoma_Hybrids_/1079548", "title"=>"Tumorigenic Potential of MSC-lung Carcinoma Hybrids.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-02-06 11:28:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/1560208"], "description"=>"<p>(<b>A</b>) MSC-lung cancer hybrids are tumorigenic and regenerate similar tumors to their respective parental lung cancer cells in NOD/SCID mice. Hematoxylin and eosin (H&E) staining performed on tumor specimens derived from parental tumor or from tumors generated by subcutaneous injection of MSC-lung cancer hybrids in NOD/SCID mice (xenograft). Data are representative of three independent experiments. (<b>B</b>) <b><i>Upper panel:</i></b> Tumorigenic potential of 1×10<sup>3</sup> A549/MSC compared with 1×10<sup>4</sup> parental A549 cells. Cells were simultaneously injected into the right (A549/MSC) and left flank (A549) of the same mouse, and the mouse photograph was taken 12 weeks after injection. <b><i>Lower panel:</i></b> Gross pathology of tumor generated by subcutaneous injection of A549/MSC hybrids in the upper panel. Data are representative of three independent experiments. Scale bar, 100 µm.</p>", "links"=>[], "tags"=>["developmental biology", "stem cells", "mesenchymal stem cells", "Molecular cell biology", "Cellular types", "oncology", "Basic cancer research", "metastasis", "Cancers and neoplasms", "Lung and intrathoracic tumors", "Cancer risk factors", "msc-lung", "cancer"], "article_id"=>1079513, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Mei-Hua Xu", "Xuan Gao", "Dan Luo", "Xiang-Dong Zhou", "Wei Xiong", "Guo-Xiang Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087893.g007", "stats"=>{"downloads"=>0, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Tumorigenic_potential_of_MSC_lung_cancer_hybrids_/1079513", "title"=>"Tumorigenic potential of MSC-lung cancer hybrids.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-06 11:28:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/1560156"], "description"=>"<p>The MSCs and lung cancer cells were fluorescently tagged by retroviral transduction with RFP- and EGFP-expressing vectors, respectively. Spontaneously-formed heterotypic hybrids expressed both EGFP and RFP. Immunostaining was performed with primary antibodies against (<b>A</b>) E-cadherin (E-Cad), (<b>B</b>) pancytokeratin (pCK), (<b>C</b>) vimentin (Vim), (<b>D</b>) α-SMA, and (<b>E</b>) fibronectin (Fibro), and revealed using AlexaFluor 647-labelled secondary antibodies (purple); nuclei were stained with DAPI (blue). Scale bar, 25 µm. (<b>F</b>) The expression levels of the mRNAs encoding E-cadherin, vimentin, α-SMA, fibronectin, Foxc2, Slug, Snail, Twist, Zeb1 and Zeb2 in spontaneously formed A549/MSC, H460/MSC, SK-MES-1/MSC heterotypic hybrids relative to respective parental lung cancer cells as determined by QRT-PCR. GAPDH mRNA was used to normalize the variability in template loading. The data are reported as mean ± SEM.</p>", "links"=>[], "tags"=>["developmental biology", "stem cells", "mesenchymal stem cells", "Molecular cell biology", "Cellular types", "oncology", "Basic cancer research", "metastasis", "Cancers and neoplasms", "Lung and intrathoracic tumors", "Cancer risk factors", "epithelial", "mesenchymal", "markers", "heterotypic", "hybrids", "respective", "cancer"], "article_id"=>1079468, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Mei-Hua Xu", "Xuan Gao", "Dan Luo", "Xiang-Dong Zhou", "Wei Xiong", "Guo-Xiang Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087893.g003", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Expression_of_epithelial_and_mesenchymal_markers_in_heterotypic_hybrids_and_respective_parental_lung_cancer_cells_/1079468", "title"=>"Expression of epithelial and mesenchymal markers in heterotypic hybrids and respective parental lung cancer cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-06 11:28:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/1560133"], "description"=>"<p>(<b>A</b>) Phase-contrast images of heterotypic hybrids and respective parental lung cancer cells. After fusion with MSCs, lung cancer cells dispersed, lost their epithelial morphology and assumed a fibroblast-like appearance with elongated shape and front-to-back polarity. Scale bar, 500 µm. (<b>B</b>) Confocal laser microscopy imaging. A549/MSC hybrids assumed a fibroblast-like appearance and expressed both EGFP and RFP. Scale bar, 25 µm.</p>", "links"=>[], "tags"=>["developmental biology", "stem cells", "mesenchymal stem cells", "Molecular cell biology", "Cellular types", "oncology", "Basic cancer research", "metastasis", "Cancers and neoplasms", "Lung and intrathoracic tumors", "Cancer risk factors", "cancer", "cells", "mscs", "morphological"], "article_id"=>1079449, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Mei-Hua Xu", "Xuan Gao", "Dan Luo", "Xiang-Dong Zhou", "Wei Xiong", "Guo-Xiang Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087893.g002", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Fusion_between_lung_cancer_cells_and_MSCs_induces_morphological_changes_/1079449", "title"=>"Fusion between lung cancer cells and MSCs induces morphological changes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-06 11:28:43"}

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  • {"unique-ip"=>"19", "full-text"=>"18", "pdf"=>"6", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"7", "cited-by"=>"0", "year"=>"2020", "month"=>"3"}
  • {"unique-ip"=>"10", "full-text"=>"14", "pdf"=>"8", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"4"}

Relative Metric

{"start_date"=>"2014-01-01T00:00:00Z", "end_date"=>"2014-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences", "average_usage"=>[291]}, {"subject_area"=>"/Biology and life sciences/Cell biology", "average_usage"=>[286]}, {"subject_area"=>"/Medicine and health sciences", "average_usage"=>[285]}]}
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Net::HTTPUnauthorized

Source
CrossRef
Time
2020-05-21 00:36:12 UTC
Target URL
http://doi.crossref.org/servlet/getForwardLinks?usr=plos&pwd=plos1&doi=10.1371%2Fjournal.pone.0087893
Trace

/app/models/concerns/networkable.rb:21:in `get_result'
/app/models/source.rb:165:in `get_data'
/app/models/retrieval_status.rb:47:in `perform_get_data'
/app/jobs/source_job.rb:52:in `block (2 levels) in perform'
/app/jobs/source_job.rb:51:in `block in perform'
/app/jobs/source_job.rb:35:in `each'
/app/jobs/source_job.rb:35:in `perform'