{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T10:02:52Z","timestamp":1785578572506,"version":"3.56.0"},"reference-count":49,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,11,11]],"date-time":"2024-11-11T00:00:00Z","timestamp":1731283200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008119","name":"Norges Milj\u00f8- og Biovitenskapelige Universitet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008119","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Vet Comparative Oncology"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Pre\u2010metastatic niche (PMN) formation is essential for metastatic development and drives organotropism. Tumour\u2010derived extracellular vesicles and soluble factors remodel the microenvironment of distant metastatic organs before subsequent metastasis. Dogs with osteosarcoma (OS) have proven to be excellent disease models for their human companions. Here, we show evidence of PMN formation in dogs with OS before metastasis. We necropsied and sampled lung tissues from dogs with naturally occurring treatment\u2010na\u00efve OS (<jats:italic>n<\/jats:italic>\u2009=\u200915) and control dogs without cancer (<jats:italic>n<\/jats:italic>\u2009=\u200910). We further divided dogs with OS into those having lung metastases (<jats:italic>n<\/jats:italic>\u2009=\u20095) and those without (<jats:italic>n<\/jats:italic>\u2009=\u200910). We stained formalin\u2010fixed paraffin\u2010embedded tissues using multiplex immunofluorescence to quantify the number of bone marrow\u2010derived cells, monocytes and macrophages in the lung samples from each dog. The numbers of CD204<jats:sup>+<\/jats:sup> macrophages, CD206<jats:sup>+<\/jats:sup> macrophages and monocytes and CD11d<jats:sup>+<\/jats:sup> bone marrow\u2010derived cells (BMDCs) were significantly higher in the pre\u2010metastatic lung of dogs with OS (<jats:italic>n<\/jats:italic>\u2009=\u200910) than in control dogs without cancer (<jats:italic>n<\/jats:italic>\u2009=\u200910). Furthermore, the total nucleated cell (DAPI<jats:sup>+<\/jats:sup>) density was higher before metastasis than in healthy lungs. In dogs with established metastases, the number of CD11d<jats:sup>+<\/jats:sup> BMDCs was significantly lower than in the pre\u2010metastatic lung, suggesting this recruitment is transient. Our study provides evidence of PMN existence in a naturally occurring cancer model similar to those observed in pre\u2010clinical murine models. BMDCs are recruited to the lungs before metastases have developed. Dogs with OS may represent ideal candidates for assessing new PMN\u2010targeting therapies.<\/jats:p>","DOI":"10.1111\/vco.13026","type":"journal-article","created":{"date-parts":[[2024,11,11]],"date-time":"2024-11-11T11:49:26Z","timestamp":1731325766000},"page":"62-72","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Immunological Pre\u2010Metastatic Niche in Dogs With Naturally Occurring Osteosarcoma"],"prefix":"10.1111","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1207-9644","authenticated-orcid":false,"given":"Mikael","family":"Kerboeuf","sequence":"first","affiliation":[{"name":"Department of Preclinical Sciences and Pathology, Faculty of Veterinary Medicine Norwegian University of Life Sciences  \u00c5s Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin Paaske","family":"Anfinsen","sequence":"additional","affiliation":[{"name":"Department of Companion Animal Clinical Sciences, Faculty of Veterinary Medicine Norwegian University of Life Sciences  \u00c5s Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erling Olaf","family":"Koppang","sequence":"additional","affiliation":[{"name":"Department of Preclinical Sciences and Pathology, Faculty of Veterinary Medicine Norwegian University of Life Sciences  \u00c5s Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frode","family":"Lingaas","sequence":"additional","affiliation":[{"name":"Department of Preclinical Sciences and Pathology, Faculty of Veterinary Medicine Norwegian University of Life Sciences  \u00c5s Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Argyle","sequence":"additional","affiliation":[{"name":"The Royal (Dick) School of Veterinary Studies and Roslin Institute University of Edinburgh  Midlothian UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon","family":"Teige","sequence":"additional","affiliation":[{"name":"Department of Preclinical Sciences and Pathology, Faculty of Veterinary Medicine Norwegian University of Life Sciences  \u00c5s Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bente Kristin","family":"S\u00e6vik","sequence":"additional","affiliation":[{"name":"AniCura Jel\u00f8y Small Animal Hospital  Moss Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Moe","sequence":"additional","affiliation":[{"name":"Department of Companion Animal Clinical Sciences, Faculty of Veterinary Medicine Norwegian University of Life Sciences  \u00c5s Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,11]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.2474"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)49915-0"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature04186"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.733627"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s43556-020-00022-z"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2016.09.011"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2753"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01433-3"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-16-0868"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-021-03873-z"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tvjl.2010.08.014"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13028-017-0341-9"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11864-009-0087-3"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.2460\/javma.1992.200.07.995"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1590\/S1413-95962004000500002"},{"issue":"1","key":"e_1_2_9_17_1","first-page":"55","article-title":"Primary Bone Rumors in the Dog: A Combined Clinical, Radiographic, and Histologic Approach to Early Diagnosis","volume":"165","author":"Ling G. V.","year":"1974","journal-title":"Journal of the American Veterinary Medical Association"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13028-021-00608-9"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-022-04262-w"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf1328"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-011-2154-9"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2007.08.001"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12032-012-0205-0"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12113457"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.155.1.35"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-40285-3"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0112770"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb3169"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.19712"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcpa.2012.06.009"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1039\/c6ib00105j"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2004.09.015"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.788365"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0183572"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tvjl.2018.02.016"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-018-0777-0"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40425-019-0622-0"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-021-00556-3"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/imm.12647"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-10-0706"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.182.1.240"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.3A0414-210R"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201444522"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-013-9381-6"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.3390\/vetsci6040083"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-2427(01)00337-3"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.08.068"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/81.12.935"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.2174\/157340711796817913"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-04843-7_17"}],"container-title":["Veterinary and Comparative Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/vco.13026","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T00:07:21Z","timestamp":1739750841000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/vco.13026"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,11]]},"references-count":49,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,3]]}},"alternative-id":["10.1111\/vco.13026"],"URL":"https:\/\/doi.org\/10.1111\/vco.13026","archive":["Portico"],"relation":{},"ISSN":["1476-5810","1476-5829"],"issn-type":[{"value":"1476-5810","type":"print"},{"value":"1476-5829","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,11]]},"assertion":[{"value":"2024-07-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}