{"doi":"10.1002/cam4.575","title":"Serum‐derived exosomes from mice with highly metastatic breast cancer transfer increased metastatic capacity to a poorly metastatic tumor","abstract":"AbstractAltered interaction between CD200 and CD200R represents an example of “checkpoint blockade” disrupting an effective, tumor‐directed, host response in murine breast cancer cells. In CD200R1KO mice, long‐term cure of EMT6 breast cancer, including metastatic spread to lung and liver, was achieved in BALB/c mice. The reverse was observed with 4THM tumors, an aggressive, inflammatory breast cancer, with increased tumor metastasis in CD200R1KO. We explored possible explanations for this difference. We measured the frequency of circulating tumor cells (CTCs) in peripheral blood of tumor bearers, as well as lung/liver and draining lymph nodes. In some cases mice received infusions of exosomes from nontumor controls, or tumor bearers, with/without additional infusions of anticytokine antibodies. The measured frequency of circulating tumor cells (CTCs) in peripheral blood was equivalent in the two models in WT and CD200R1KO mice. Increased metastasis in EMT6 tumor bearers was seen in vivo following adoptive transfer of serum, or serum‐derived exosomes, from 4THM tumor bearers, an effect which was attenuated by anti‐IL‐6, and anti‐IL‐17, but not anti‐TNFα, antibody. Anti‐IL‐6 also attenuated enhanced migration of EMT6 cells in vitro induced by 4THM serum or exosomes, or recombinant IL‐6. Exosome cytokine proteomic profiles responses in 4THM and EMT6 tumor‐bearing mice were regulated by CD200:CD200R interactions, with attenuation of both IL‐6 and IL‐17 in 4THM CD200tg mice, and enhanced levels in 4THM CD200R1KO mice. We suggest these cytokines act on the microenvironment at sites within the host, and/or directly on tumor cells themselves, to increase metastatic potential.","journal":"Cancer Medicine","year":2016,"id":596175,"datarank":0.5050943744979712,"base_score":3.367295829986474,"endowment":3.367295829986474,"self_citation_contribution":0.5050943744979712,"citation_network_contribution":0.0,"self_endowment_contribution":0.5050943744979712,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":28,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":8,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1526748,"name":"Nuray Erin","orcid":null,"position":1,"is_corresponding":false},{"id":753373,"name":"Fang Zhu","orcid":"0000-0002-6676-1270","position":2,"is_corresponding":false},{"id":1526747,"name":"Reginald M. Gorczynski","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Serum‐derived exosomes from mice with highly metastatic breast cancer transfer increased metastatic capacity to a poorly metastatic tumor","abstract":"AbstractAltered interaction between CD200 and CD200R represents an example of “checkpoint blockade” disrupting an effective, tumor‐directed, host response in murine breast cancer cells. In CD200R1KO mice, long‐term cure of EMT6 breast cancer, including metastatic spread to lung and liver, was achieved in BALB/c mice. The reverse was observed with 4THM tumors, an aggressive, inflammatory breast cancer, with increased tumor metastasis in CD200R1KO. We explored possible explanations for this difference. We measured the frequency of circulating tumor cells (CTCs) in peripheral blood of tumor bearers, as well as lung/liver and draining lymph nodes. In some cases mice received infusions of exosomes from nontumor controls, or tumor bearers, with/without additional infusions of anticytokine antibodies. The measured frequency of circulating tumor cells (CTCs) in peripheral blood was equivalent in the two models in WT and CD200R1KO mice. Increased metastasis in EMT6 tumor bearers was seen in vivo following adoptive transfer of serum, or serum‐derived exosomes, from 4THM tumor bearers, an effect which was attenuated by anti‐IL‐6, and anti‐IL‐17, but not anti‐TNFα, antibody. Anti‐IL‐6 also attenuated enhanced migration of EMT6 cells in vitro induced by 4THM serum or exosomes, or recombinant IL‐6. Exosome cytokine proteomic profiles responses in 4THM and EMT6 tumor‐bearing mice were regulated by CD200:CD200R interactions, with attenuation of both IL‐6 and IL‐17 in 4THM CD200tg mice, and enhanced levels in 4THM CD200R1KO mice. We suggest these cytokines act on the microenvironment at sites within the host, and/or directly on tumor cells themselves, to increase metastatic potential.","is_dataset_classified":null,"base_score":3.367295829986474,"endowment":3.367295829986474,"datacite_reuse_total":8,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"26725371","pmcid":"PMC4735763","openalex_id":"https://openalex.org/W2222925888","authors":[],"funders":[{"funder_name":"Canadian Institutes of Health Research","grant_id":"MOP‐106447","title":null},{"funder_name":"Canadian Institutes of Health Research","grant_id":"MOP-106447","title":null}],"total_grants":2,"fwci":1.7635,"citation_percentile":0.84165878,"influential_citations":1,"citation_trend":[{"year":2014,"count":1},{"year":2016,"count":2},{"year":2017,"count":4},{"year":2018,"count":2},{"year":2019,"count":3},{"year":2020,"count":10},{"year":2022,"count":2},{"year":2023,"count":2},{"year":2024,"count":2}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/cam4.575","host_type":"journal"},{"url":"https://doi.org/10.1002/cam4.575","host_type":"GOLD"},{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/cam4.575","host_type":"publisher"},{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fcam4.575","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1002/cam4.575","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/full-xml/10.1002/cam4.575","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/26725371","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4735763","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC4735763","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC4735763?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Extracellular vesicles in disease","Immunotherapy and Immune Responses","Cancer Cells and Metastasis","Medicine","Biology","Animals","Antigens, CD","Breast Neoplasms","Cell Line, Tumor","Cell Movement","Cytokines","Disease Models, Animal","Exosomes","Female","Membrane Glycoproteins","Mice","Mice, Knockout","Mice, Transgenic","Neoplasm Metastasis","Neoplastic Cells, Circulating"],"mesh_terms":["Animals","Breast Neoplasms","Cell Movement","Disease Models, Animal","Female","Membrane Glycoproteins","Mice, Transgenic","Neoplastic Cells, Circulating","Neoplasm Metastasis","Antigens, CD","Cytokines","Mice, Knockout","Cell Line, Tumor","Mice","Exosomes"],"keywords":["Microvesicles","Medicine","Metastasis","Metastatic breast cancer","Cancer research","Exosome","Tumor M2-PK","Adoptive cell transfer","Cancer","In vivo","Primary tumor","Breast cancer","Tumor microenvironment","Circulating tumor cell","Antibody","Immunology","Immune system","Internal medicine","Biology","T cell","Tumor marker","microRNA","Immunotherapy","Serum Factors","Cd200:cd200r"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[{"doi":"10.6084/m9.figshare.13279115.v1","title":"Additional file 1 of Extracellular vesicles from young women’s breast cancer patients drive increased invasion of non-malignant cells via the Focal Adhesion Kinase pathway: a proteomic approach","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.13279115","title":"Additional file 1 of Extracellular vesicles from young women’s breast cancer patients drive increased invasion of non-malignant cells via the Focal Adhesion Kinase pathway: a proteomic approach","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.13279118.v1","title":"Additional file 2 of Extracellular vesicles from young women’s breast cancer patients drive increased invasion of non-malignant cells via the Focal Adhesion Kinase pathway: a proteomic approach","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.13279118","title":"Additional file 2 of Extracellular vesicles from young women’s breast cancer patients drive increased invasion of non-malignant cells via the Focal Adhesion Kinase pathway: a proteomic approach","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.13279121.v1","title":"Additional file 3 of Extracellular vesicles from young women’s breast cancer patients drive increased invasion of non-malignant cells via the Focal Adhesion Kinase pathway: a proteomic approach","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.13279121","title":"Additional file 3 of Extracellular vesicles from young women’s breast cancer patients drive increased invasion of non-malignant cells via the Focal Adhesion Kinase pathway: a proteomic approach","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.13279124.v1","title":"Additional file 4 of Extracellular vesicles from young women’s breast cancer patients drive increased invasion of non-malignant cells via the Focal Adhesion Kinase pathway: a proteomic approach","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.13279124","title":"Additional file 4 of Extracellular vesicles from young women’s breast cancer patients drive increased invasion of non-malignant cells via the Focal Adhesion Kinase pathway: a proteomic approach","publisher":"figshare","resource_type":"JournalArticle"}],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-28T04:33:57.672277Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}