Residual Tumor Cells That Drive Disease Relapse after Chemotherapy Do Not Have Enhanced Tumor Initiating Capacity
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{"title"=>"Residual Tumor Cells That Drive Disease Relapse after Chemotherapy Do Not Have Enhanced Tumor Initiating Capacity", "type"=>"journal", "authors"=>[{"first_name"=>"Ganapati V.", "last_name"=>"Hegde", "scopus_author_id"=>"14833744500"}, {"first_name"=>"Cecile", "last_name"=>"de la Cruz", "scopus_author_id"=>"55440577900"}, {"first_name"=>"Jeffrey", "last_name"=>"Eastham-Anderson", "scopus_author_id"=>"15842970300"}, {"first_name"=>"Yanyan", "last_name"=>"Zheng", "scopus_author_id"=>"55601827400"}, {"first_name"=>"E. Alejandro", "last_name"=>"Sweet-Cordero", "scopus_author_id"=>"8597063800"}, {"first_name"=>"Erica L.", "last_name"=>"Jackson", "scopus_author_id"=>"7202526421"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "pui"=>"365952118", "doi"=>"10.1371/journal.pone.0045647", "sgr"=>"84868116554", "scopus"=>"2-s2.0-84868116554", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "pmid"=>"23115623"}, "id"=>"b3dda439-a4d0-3507-9039-10fb9bc5e8bd", "abstract"=>"Although chemotherapy is used to treat most advanced solid tumors, recurrent disease is still the major cause of cancer-related mortality. Cancer stem cells (CSCs) have been the focus of intense research in recent years because they provide a possible explanation for disease relapse. However, the precise role of CSCs in recurrent disease remains poorly understood and surprisingly little attention has been focused on studying the cells responsible for re-initiating tumor growth within the original host after chemotherapy treatment. We utilized both xenograft and genetically engineered mouse models of non-small cell lung cancer (NSCLC) to characterize the residual tumor cells that survive chemotherapy treatment and go on to cause tumor regrowth, which we refer to as tumor re-initiating cells (TRICs). We set out to determine whether TRICs display characteristics of CSCs, and whether assays used to define CSCs also provide an accurate readout of a cell's ability to cause tumor recurrence. We did not find consistent enrichment of CSC marker positive cells or enhanced tumor initiating potential in TRICs. However, TRICs from all models do appear to be in EMT, a state that has been linked to chemoresistance in numerous types of cancer. Thus, the standard CSC assays may not accurately reflect a cell's ability to drive disease recurrence.", "link"=>"http://www.mendeley.com/research/residual-tumor-cells-drive-disease-relapse-after-chemotherapy-not-enhanced-tumor-initiating-capacity", "reader_count"=>26, "reader_count_by_academic_status"=>{"Student > Doctoral Student"=>2, "Researcher"=>8, "Student > Ph. D. Student"=>6, "Student > Postgraduate"=>1, "Student > Master"=>4, "Student > Bachelor"=>1, "Lecturer"=>1, "Professor"=>2, "Unspecified"=>1}, "reader_count_by_user_role"=>{"Student > Doctoral Student"=>2, "Researcher"=>8, "Student > Ph. D. Student"=>6, "Student > Postgraduate"=>1, "Student > Master"=>4, "Student > Bachelor"=>1, "Lecturer"=>1, "Professor"=>2, "Unspecified"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>3, "Agricultural and Biological Sciences"=>15, "Medicine and Dentistry"=>4, "Physics and Astronomy"=>1, "Chemistry"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>4}, "Chemistry"=>{"Chemistry"=>1}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>15}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Unspecified"=>{"Unspecified"=>2}}, "reader_count_by_country"=>{"United States"=>1, "Denmark"=>1, "Spain"=>1}, "group_count"=>3}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/553694"], "description"=>"<p>(A) Schematic representation of study design. GFP labeled human tumor cells were transplanted subcutaneously, and when tumor size reached ∼250 mm<sup>3</sup> mice were treated with either vehicle or chemotherapy as shown in the respective models. GFP+ tumor cells were isolated from regressed or vehicle-treated tumors by FACS-sorting after enzymatic digestion and dissociation. Tumors were collected a minimum of one week after the last dose of chemotherapy and before the resumption of tumor growth. (B) Growth of vehicle and chemo-treated Calu3-GFP xenograft tumors. Data presented as mean tumor volume ± SEM, n = 15/group. (C) Growth of vehicle and chemo-treated H441-GFP xenograft tumors. Data presented as mean tumor volume ± SEM, n = 9/group for vehicle-treated and n = 14/group for chemo-treated. (D) Growth of vehicle and chemo-treated H596-GFP xenograft tumors. Data presented as mean tumor volume ± SEM, n = 10/group for vehicle-treated and n = 18/group for chemo-treated. Each/indicates a mouse euthanized for analysis. (E) Number of GFP+ tumor cells present in vehicle and chemo-treated tumors as determined by FACS. Sorting of vehicle-treated tumor cells was stopped at 500,000 cells for all models.</p>", "links"=>[], "tags"=>["models", "re-initiating", "cells"], "article_id"=>224180, "categories"=>["Cancer", "Cell Biology"], "users"=>["Ganapati V. Hegde", "Cecile de la Cruz", "Jeffrey Eastham-Anderson", "Yanyan Zheng", "E. Alejandro Sweet-Cordero", "Erica L. Jackson"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0045647.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Characterization_of_In_vivo_Models_for_the_Study_of_Tumor_Re_Initiating_Cells_TRICs_/224180", "title"=>"Characterization of <i>In vivo</i> Models for the Study of Tumor Re-Initiating Cells (TRICs).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 21:16:17"}
  • {"files"=>["https://ndownloader.figshare.com/files/553813"], "description"=>"<p>(A) Proportion of CSC-marker positive cells in vehicle and chemotherapy-treated Calu3, H441 and H596 tumors. Data is presented as average +/− SEM, n ≥4 mice per group. (B–D) Tumor forming capacity of B) Calu3-GFP, C) H441-GFP and D) H596-GFP tumor cells. Cells were isolated from vehicle or chemo-treated mice at tumor regression and grafted subcutaneously into athymic nude mice. Graphs show indivdual tumor size with bars indicating average tumor volume per group (left) and tumor incidence (right). Tumors >50 mm<sup>3</sup> were considered as positive tumor growth. (E) Tumor forming capacity of GEMM tumor cells isolated from vehicle or chemo treated mice at tumor regression and grafted orthotopically into athymic nude mice. Graphs show number of tumors per individual mouse with bars indicating average number (left) and tumor incidence (right). (For further details see also <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0045647#pone-0045647-t001\" target=\"_blank\">Table 1</a>).</p>", "links"=>[], "tags"=>["trics", "cancer"], "article_id"=>224307, "categories"=>["Cancer", "Cell Biology"], "users"=>["Ganapati V. Hegde", "Cecile de la Cruz", "Jeffrey Eastham-Anderson", "Yanyan Zheng", "E. Alejandro Sweet-Cordero", "Erica L. Jackson"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0045647.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Characterization_of_TRICs_for_Cancer_Stem_Cell_Potential_in_vivo_/224307", "title"=>"Characterization of TRICs for Cancer Stem Cell Potential <i>in vivo</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 21:16:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/554136"], "description"=>"<p>A) Masson’s Trichrome staining of vehicle and regressed chemo-treated tumors showing a decrease in tumor cells (red) and an increase in collagen-containing stromal cells (blue) in residual tumors. B) FACS analysis of vehicle and regressed tumors showing a decreased tumor:stroma ratio in residual tumors.</p>", "links"=>[], "tags"=>["stromal", "residual", "chemotherapy-treated"], "article_id"=>224624, "categories"=>["Cancer", "Cell Biology"], "users"=>["Ganapati V. Hegde", "Cecile de la Cruz", "Jeffrey Eastham-Anderson", "Yanyan Zheng", "E. Alejandro Sweet-Cordero", "Erica L. Jackson"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0045647.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Increased_Stromal_Component_in_Residual_Chemotherapy_Treated_Tumors_/224624", "title"=>"Increased Stromal Component in Residual Chemotherapy-Treated Tumors.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 21:18:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/554341"], "description"=>"<p>A) Representative FACS plots showing gates used for sorting GFP+ tumor and stromal cells from Calu3 (left) and H441 tumors (right). B) Calu-3 and C) H441 tumor (GFP+) and stromal (GFP-) cells were isolated from tumors taken from vehicle or chemo-treated mice at tumor regression. Tumor and stromal cells were mixed as indicated and grafted subcutaneously into athymic nude mice. Graphs show individual tumor volumes at the end of study, bars indicate the average tumor volume per group. See <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0045647#pone-0045647-t002\" target=\"_blank\">Table 2</a> for further details.</p>", "links"=>[], "tags"=>["stroma", "initiating", "trics", "transplanation"], "article_id"=>224833, "categories"=>["Cancer", "Cell Biology"], "users"=>["Ganapati V. Hegde", "Cecile de la Cruz", "Jeffrey Eastham-Anderson", "Yanyan Zheng", "E. Alejandro Sweet-Cordero", "Erica L. Jackson"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0045647.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_Stroma_on_Tumor_Initiating_Potential_of_TRICs_in_transplanation_assays_/224833", "title"=>"Effect of Stroma on Tumor Initiating Potential of TRICs in transplanation assays.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 21:19:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/554518"], "description"=>"<p>(A) Expression of EMT markers and EMT-driving transcription factors in Calu3-GFP and H441-GFP tumor cells isolated from vehicle or chemo treated mice at tumor regression was assessed by qRT-PCR. (B–C) Proportions of E-Cadherin and Vimentin expressing tumor cells were determined by immunofluorescence analysis in B) Calu3-GFP and C) H441-GFP tumors. Sections were co-stained for GFP and E-Cadherin or GFP and Vimentin. Data are expressed as average+/−SEM. (D–E) Correlation between the time course of chemotherapy-induced cell death (D) and expression of EMT-drivers as determined by qRT-PCR (E) Presented expression levels are relative to time-matched vehicle-treated controls.</p>", "links"=>[], "tags"=>["cell biology", "oncology"], "article_id"=>225010, "categories"=>["Cancer", "Cell Biology"], "users"=>["Ganapati V. Hegde", "Cecile de la Cruz", "Jeffrey Eastham-Anderson", "Yanyan Zheng", "E. Alejandro Sweet-Cordero", "Erica L. Jackson"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0045647.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_TRICs_are_in_a_state_of_EMT_/225010", "title"=>"TRICs are in a state of EMT.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 21:20:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/554652"], "description"=>"<p>VT = Tumor cells from vehicle-treated mice, CT = Tumor cells from chemo-treated mice at regression, VS = Stromal cells from vehicle-treated mice, and CS = Stromal cells from chemo-treated mice at regression. Tumor size of >50 mm<sup>3</sup> was considered as positive for tumor growth.</p>", "links"=>[], "tags"=>["stroma", "tumor-initiating", "trics", "transplantation"], "article_id"=>225142, "categories"=>["Cancer", "Cell Biology"], "users"=>["Ganapati V. Hegde", "Cecile de la Cruz", "Jeffrey Eastham-Anderson", "Yanyan Zheng", "E. Alejandro Sweet-Cordero", "Erica L. Jackson"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0045647.t002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_stroma_on_tumor_initiating_potential_of_TRICs_in_transplantation_assays_/225142", "title"=>"Effect of stroma on tumor-initiating potential of TRICs in transplantation assays.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-19 21:21:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/554680"], "description"=>"<p>Tumor size >50 mm<sup>3</sup> was considered as positive for tumor growth.</p>", "links"=>[], "tags"=>["initiating", "trics", "transplantation"], "article_id"=>225173, "categories"=>["Cancer", "Cell Biology"], "users"=>["Ganapati V. Hegde", "Cecile de la Cruz", "Jeffrey Eastham-Anderson", "Yanyan Zheng", "E. Alejandro Sweet-Cordero", "Erica L. Jackson"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0045647.t001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Tumor_initiating_potential_of_TRICs_in_transplantation_assays_/225173", "title"=>"Tumor initiating potential of TRICs in transplantation assays.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-19 21:21:37"}

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Relative Metric

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