{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T09:53:26Z","timestamp":1791194006224,"version":"4.1.0"},"reference-count":61,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T00:00:00Z","timestamp":1790985600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Midnight Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>Both canine hemangiosarcoma and human angiosarcoma are aggressive malignancies characterized by clinical and molecular heterogeneity. Current in vitro models rely on individual cell lines, failing to capture this biological complexity. We established a standardized 2D in vitro platform comprising a panel of three canine primary splenic hemangiosarcoma cell lines (EMN009, EMN011, EMN017) and one patient-matched brain metastasis (EMN010) evaluated in parallel. Using gold-standard assays\u2014morphometrics, growth, migration and tube-formation assays\u2014alongside disease-relevant transcriptomic and microRNA profiling, we characterized this multi-line system under harmonized conditions. Neoplastic lines shared a robust core angiogenic signature of 42 overexpressed genes linked to VEGF, AGE-RAGE, and S1P signaling, and a 47-gene cancer stem cell engine enriched in the Hippo\/YAP1 pathway. Transcriptomic clustering divided the lines into slower-growing primary tumors (EMN009\/EMN011) and highly angiogenic phenotypes (EMN017\/EMN010). Isogenic comparison revealed that the metastatic EMN010 uniquely upregulates STAT signaling and peptidyl-tyrosine phosphorylation. MicroRNA profiling demonstrated a global downregulation of tumor-suppressors miR-126-5p and miR-452-5p, unleashing VEGFA-driven angiogenesis, while visceral hemangiosarcoma biomarker miR-214-3p was significantly upregulated. Conversely, miR-10b and miR-133-3p expression varied across lines, reflecting ongoing clonal evolution. This integrated platform successfully recapitulates hemangiosarcoma heterogeneity, providing a reliable, standardized framework for comparative oncology and targeted pathophysiological studies.<\/jats:p>","DOI":"10.3390\/ani16193109","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T08:57:18Z","timestamp":1791190638000},"page":"3109","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Canine Hemangiosarcoma Cell Lines In Vitro Platform Captures Morphological, Functional, and Molecular Diversity"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-3901-7799","authenticated-orcid":false,"given":"Lucia","family":"di Caporiacco","sequence":"first","affiliation":[{"name":"IRET Foundation ETS, Ozzano Emilia, 40064 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Francesca","family":"Merighi","sequence":"additional","affiliation":[{"name":"Health Science and Technologies Interdepartmental Center for Industrial Research (HST-ICIR), University of Bologna, 40064 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Luciana","family":"Giardino","sequence":"additional","affiliation":[{"name":"Health Science and Technologies Interdepartmental Center for Industrial Research (HST-ICIR), University of Bologna, 40064 Bologna, Italy"},{"name":"Department of Veterinary Medical Sciences, University of Bologna, 40064 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7843-615X","authenticated-orcid":false,"given":"Laura","family":"Marconato","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medical Sciences, University of Bologna, 40064 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1020-4261","authenticated-orcid":false,"given":"Vito Antonio","family":"Baldassarro","sequence":"additional","affiliation":[{"name":"Health Science and Technologies Interdepartmental Center for Industrial Research (HST-ICIR), University of Bologna, 40064 Bologna, Italy"},{"name":"Department of Veterinary Medical Sciences, University of Bologna, 40064 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4426-8477","authenticated-orcid":false,"given":"Laura","family":"Calz\u00e0","sequence":"additional","affiliation":[{"name":"Health Science and Technologies Interdepartmental Center for Industrial Research (HST-ICIR), University of Bologna, 40064 Bologna, Italy"},{"name":"Department of Pharmacy and Biotechnology, University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0302-3027","authenticated-orcid":false,"given":"Corinne","family":"Quadalti","sequence":"additional","affiliation":[{"name":"Health Science and Technologies Interdepartmental Center for Industrial Research (HST-ICIR), University of Bologna, 40064 Bologna, Italy"},{"name":"Department of Pharmacy and Biotechnology, University of Bologna, 40126 Bologna, 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Vet. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"De Nardi, A.B., de Oliveira Massoco Salles Gomes, C., Fonseca-Alves, C.E., de Paiva, F.N., Linhares, L.C.M., Carra, G.J.U., Horta, R.D.S., Sueiro, F.A.R., Jark, P.C., and Nishiya, A.T. (2023). Diagnosis, Prognosis, and Treatment of Canine Hemangiosarcoma: A Review Based on a Consensus Organized by the Brazilian Association of Veterinary Oncology, ABROVET. Cancers, 15.","DOI":"10.3390\/cancers15072025"},{"key":"ref_3","first-page":"2303","article-title":"Angiosarcoma: A review of diagnosis and current treatment","volume":"9","author":"Cao","year":"2019","journal-title":"Am. J. Cancer Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1623327","DOI":"10.3389\/fonc.2025.1623327","article-title":"Angiosarcoma: A systematic review of biomarkers in diagnosis, prognosis, and therapeutic strategies","volume":"15","author":"Luong","year":"2025","journal-title":"Front. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e585","DOI":"10.1002\/vetr.585","article-title":"Canine and feline haemangiosarcoma","volume":"189","author":"Griffin","year":"2021","journal-title":"Vet. Rec."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Leach, E., Jafari, A., Torbenson, E., Hsia, B., and Tauseef, A. (2025). Genomic and Demographic Characteristics of Angiosarcoma as Described in the AACR Project GENIE Registry. Cancers, 17.","DOI":"10.3390\/cancers17223663"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"9960085","DOI":"10.1155\/2021\/9960085","article-title":"Localized Angiosarcoma, Not One Disease: A Retrospective Single-Center Study on Prognosis Depending on the Primary Site and Etiology","volume":"2021","author":"Schott","year":"2021","journal-title":"Sarcoma"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Wang, G., Wu, M., Durham, A.C., Radaelli, E., Mason, N.J., Xu, X., and Roth, D.B. (2020). Molecular subtypes in canine hemangiosarcoma reveal similarities with human angiosarcoma. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0229728"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1016\/j.ajpath.2013.12.025","article-title":"Identification of three molecular and functional subtypes in canine hemangiosarcoma through gene expression profiling and progenitor cell characterization","volume":"184","author":"Gorden","year":"2014","journal-title":"Am. J. Pathol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/0021-9975(78)90012-9","article-title":"Haemangiosarcoma in dogs","volume":"88","author":"Oksanen","year":"1978","journal-title":"J. Comp. Pathol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1111\/j.1939-165X.2005.tb00005.x","article-title":"Canine angiosarcoma: Cytologic, histologic, and immunohistochemical correlations","volume":"34","author":"Bertazzolo","year":"2005","journal-title":"Vet. Clin. Pathol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1002\/cncy.21726","article-title":"Cytologic features of angiosarcoma: A review of 26 cases diagnosed on FNA","volume":"124","author":"Geller","year":"2016","journal-title":"Cancer Cytopathol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Wong, S., Ehrhart, E.J., Stewart, S., Zismann, V., Cawley, J., Halperin, R., Briones, N., Richter, K., Sivaprakasam, K., and Perdigones, N. (2022). Genomic landscapes of canine splenic angiosarcoma (hemangiosarcoma) contain extensive heterogeneity within and between patients. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0264986"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1250766","DOI":"10.3389\/fonc.2023.1250766","article-title":"Hemangiosarcoma in dogs as a potential non-rodent animal model for drug discovery research of angiosarcoma in humans","volume":"13","author":"Heishima","year":"2023","journal-title":"Front. Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2410","DOI":"10.1158\/1541-7786.MCR-19-0221","article-title":"Comparative Genomics Reveals Shared Mutational Landscape in Canine Hemangiosarcoma and Human Angiosarcoma","volume":"17","author":"Megquier","year":"2019","journal-title":"Mol. Cancer Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1158\/1541-7786.MCR-20-0937","article-title":"Genomically Complex Human Angiosarcoma and Canine Hemangiosarcoma Establish Convergent Angiogenic Transcriptional Programs Driven by Novel Gene Fusions","volume":"19","author":"Kim","year":"2021","journal-title":"Mol. Cancer Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1530","DOI":"10.2460\/javma.234.12.1530","article-title":"One medicine, one pathology, and the one health concept","volume":"234","author":"Sundberg","year":"2009","journal-title":"J. Am. Vet. Med. Assoc."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.rvsc.2005.09.005","article-title":"Biological and molecular characterization of a canine hemangiosarcoma-derived cell line","volume":"81","author":"Thamm","year":"2006","journal-title":"Res. Vet. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Hynds, R.E., Vladimirou, E., and Janes, S.M. (2018). The Secret Lives of Cancer Cell Lines. Disease Models & Mechanisms, The Company of Biologists Ltd.","DOI":"10.1242\/dmm.037366"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Urz\u00ec, O., Gasparro, R., Costanzo, E., De Luca, A., Giavaresi, G., Fontana, S., and Alessandro, R. (2023). Three-Dimensional Cell Cultures: The Bridge between In Vitro and In Vivo Models. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241512046"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"\u0141azarczyk, M., Mickael, M.E., Skiba, D., Kurzejamska, E., \u0141awi\u0144ski, M., Horba\u0144czuk, J.O., Radziszewski, J., Fraczek, K., Wolinska, R., and Paszkiewicz, J. (2023). The Journey of Cancer Cells to the Brain: Challenges and Opportunities. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24043854"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3820","DOI":"10.1002\/cam4.1667","article-title":"Emerging findings into molecular mechanism of brain metastasis","volume":"7","author":"Ni","year":"2018","journal-title":"Cancer Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1038\/labinvest.3700080","article-title":"Canine malignant hemangiosarcoma as a model of primitive angiogenic endothelium","volume":"84","author":"Fosmire","year":"2004","journal-title":"Lab Investig."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: An open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"11568","DOI":"10.1038\/s41598-020-67289-8","article-title":"Angiogenesis Analyzer for ImageJ\u2014A comparative morphometric analysis of \u201cEndothelial Tube Formation Assay\u201d and \u201cFibrin Bead Assay","volume":"10","author":"Carpentier","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Suarez-Arnedo, A., Figueroa, F.T., Clavijo, C., Arbel\u00e1ez, P., Cruz, J.C., and Mu\u00f1oz-Camargo, C. (2020). An image J plugin for the high throughput image analysis of in vitro scratch wound healing assays. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0232565"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"dmm049044","DOI":"10.1242\/dmm.049044","article-title":"Comparison of the oncogenomic landscape of canine and feline hemangiosarcoma shows novel parallels with human angiosarcoma","volume":"14","author":"Wong","year":"2021","journal-title":"Dis. Model. Mech."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1016\/j.exphem.2006.04.013","article-title":"Canine hemangiosarcoma originates from hematopoietic precursors with potential for endothelial differentiation","volume":"34","author":"Helm","year":"2006","journal-title":"Exp. Hematol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1158\/2767-9764.CRC-23-0441","article-title":"Hemangiosarcoma Cells Promote Conserved Host-derived Hematopoietic Expansion","volume":"4","author":"Kim","year":"2024","journal-title":"Cancer Res. Commun."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"187","DOI":"10.3389\/fgene.2017.00187","article-title":"The AGE-RAGE Axis: Implications for Age-Associated Arterial Diseases","volume":"8","author":"Senatus","year":"2017","journal-title":"Front. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"812","DOI":"10.37349\/etat.2023.00170","article-title":"AGEs and RAGE: Metabolic and molecular signatures of the glycation-inflammation axis in malignant or metastatic cancers","volume":"4","author":"Palanissami","year":"2023","journal-title":"Explor. Target. Antitumor Ther."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1038\/s41392-024-01764-w","article-title":"TGF-\u03b2 signaling in health, disease, and therapeutics","volume":"9","author":"Deng","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1038\/modpathol.2013.56","article-title":"Active TGF-\u03b2 signaling and decreased expression of PTEN separates angiosarcoma of bone from its soft tissue counterpart","volume":"26","author":"Verbeke","year":"2013","journal-title":"Mod. Pathol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"388","DOI":"10.3390\/vetsci2040388","article-title":"Pathobiology of Hemangiosarcoma in Dogs: Research Advances and Future Perspectives","volume":"2","author":"Kim","year":"2015","journal-title":"Vet. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/S0344-0338(00)80041-2","article-title":"Overexpression of Ets-1 transcription factor in angiosarcoma of the skin","volume":"196","author":"Naito","year":"2000","journal-title":"Pathol. Res. Pract."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1046\/j.1365-4362.2000.00950.x","article-title":"The urokinase plasminogen activator system in angiosarcoma, Kaposi\u2019s sarcoma, granuloma pyogenicum, and angioma: An immunohistochemical study","volume":"39","author":"Thewes","year":"2000","journal-title":"Int. J. Dermatol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3472","DOI":"10.1016\/j.celrep.2019.11.036","article-title":"Sphingosine-1-Phosphate Receptor 1 Activity Promotes Tumor Growth by Amplifying VEGF-VEGFR2 Angiogenic Signaling","volume":"29","author":"Anwar","year":"2019","journal-title":"Cell Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.yexcr.2014.02.020","article-title":"Interleukin-8 promotes canine hemangiosarcoma growth by regulating the tumor microenvironment","volume":"323","author":"Kim","year":"2014","journal-title":"Exp. Cell Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1038\/s41591-018-0044-4","article-title":"STAT3 labels a subpopulation of reactive astrocytes required for brain metastasis","volume":"24","author":"Priego","year":"2018","journal-title":"Nat. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1158\/1078-0432.CCR-13-2010","article-title":"Oxford and the Savannah: Can the hippo provide an explanation for Peto\u2019s paradox?","volume":"20","author":"Kelleher","year":"2014","journal-title":"Clin. Cancer Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4147","DOI":"10.21873\/anticanres.17245","article-title":"Role of the Hippo-YAP\/TAZ Pathway in Epithelioid Hemangioendothelioma and its Potential as a Therapeutic Target","volume":"44","author":"Suto","year":"2024","journal-title":"Anticancer Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2295","DOI":"10.1111\/cas.13379","article-title":"Survivin: A novel marker and potential therapeutic target for human angiosarcoma","volume":"108","author":"Tsuneki","year":"2017","journal-title":"Cancer Sci."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Salguero-Aranda, C., Olmedo-Pelayo, J., de \u00c1lava, E., Amaral, A.T., and D\u00edaz-Mart\u00edn, J. (2022). Genetic Alterations and Deregulation of Hippo Pathway as a Pathogenetic Mechanism in Bone and Soft Tissue Sarcoma. Cancers, 14.","DOI":"10.3390\/cancers14246211"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Giuliano, A., Horta, R.S., Vieira, R.A.M., Hume, K.R., and Dobson, J. (2022). Repurposing Drugs in Small Animal Oncology. Animals, 13.","DOI":"10.3390\/ani13010139"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1522705","DOI":"10.3389\/fcell.2025.1522705","article-title":"YAP\/TAZ-associated cell signaling\u2014At the crossroads of cancer and neurodevelopmental disorders","volume":"13","author":"Ajongbolo","year":"2025","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Pinto, M., Violante, S., Casc\u00e3o, R., and Faria, C.C. (2025). Unlocking the Role of Metabolic Pathways in Brain Metastatic Disease. Cells, 14.","DOI":"10.3390\/cells14100707"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Zoroddu, S., Lucariello, A., De Luca, A., and Bagella, L. (2024). Dysregulation of miRNAs in Soft Tissue Sarcomas. Cells, 13.","DOI":"10.3390\/cells13221853"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1385632","DOI":"10.3389\/fonc.2024.1385632","article-title":"MicroRNAs and angiosarcoma: Are there promising reports?","volume":"14","author":"Afrooghe","year":"2024","journal-title":"Front. Oncol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1111\/vco.12949","article-title":"Dysregulated miRNAs in a canine model of haemangiosarcoma metastatic to the brain","volume":"22","author":"Sabattini","year":"2024","journal-title":"Vet. Comp. Oncol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1177\/03009858251317466","article-title":"MicroRNAs in serum and tissue can differentiate splenic hemangiosarcoma from other splenic masses in dogs","volume":"62","author":"Ludwig","year":"2025","journal-title":"Vet. Pathol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"659","DOI":"10.2460\/ajvr.82.8.659","article-title":"Identification of serum microRNAs with differential expression between dogs with splenic masses and healthy dogs with histologically normal spleens","volume":"82","author":"Grimes","year":"2021","journal-title":"Am. J. Vet. Res."},{"key":"ref_52","first-page":"1","article-title":"A panel of 4 circulating microRNAs (126-5p, 150\u2013155p, 452\u2013455p, and 543) discriminates dogs with splenic hemangiosarcoma from those with noncancerous splenic masses","volume":"1","author":"Grimes","year":"2025","journal-title":"Am. J. Vet. Res."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Grimes, J.A., and Schmiedt, J.M. (2025). Circulating levels of microRNAs 126-5p, 150\u2013155p, 214\u20133p, and 452-5p decrease following splenectomy in dogs with hemangiosarcoma. Am. J. Vet. Res., 87.","DOI":"10.2460\/ajvr.25.07.0250"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Grimes, J.A., Prasad, N., Levy, S., Cattley, R., Lindley, S., Boothe, H.W., Henderson, R.A., and Smith, B.F. (2016). A comparison of microRNA expression profiles from splenic hemangiosarcoma, splenic nodular hyperplasia, and normal spleens of dogs. BMC Vet. Res., 12.","DOI":"10.1186\/s12917-016-0903-5"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.devcel.2008.07.008","article-title":"miR-126 regulates angiogenic signaling and vascular integrity","volume":"15","author":"Fish","year":"2008","journal-title":"Dev. Cell"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Mo, J.S., Park, W.C., Choi, S.-C., Yun, K.J., and Chae, S.-C. (2019). MicroRNA 452 Regulates Cell Proliferation, Cell Migration, and Angiogenesis in Colorectal Cancer by Suppressing VEGFA Expression. Cancers, 11.","DOI":"10.3390\/cancers11101613"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"25377","DOI":"10.3390\/ijms161025377","article-title":"MicroRNA-214 and MicroRNA-126 Are Potential Biomarkers for Malignant Endothelial Proliferative Diseases","volume":"16","author":"Heishima","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Tamburini, B.A., Trapp, S., Phang, T.L., Schappa, J.T., Hunter, L.E., and Modiano, J.F. (2009). Gene expression profiles of sporadic canine hemangiosarcoma are uniquely associated with breed. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0005549"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"16442","DOI":"10.1038\/s41598-025-89862-9","article-title":"Real-world evidence couples genomic biomarkers with therapeutic outcomes for canine hemangiosarcoma","volume":"15","author":"Rodrigues","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Baldassarro, V.A. (2021). High-content screening differentiation and maturation analysis of fetal and adult neural stem cell-derived oligodendrocyte precursor cell cultures. J. Vis. Exp., e61988.","DOI":"10.3791\/61988"},{"key":"ref_61","first-page":"671","article-title":"Vulnerability of primary neurons derived from Tg2576 Alzheimer mice to oxygen and glucose deprivation: Role of intraneuronal amyloid-\u03b2 accumulation and astrocytes","volume":"10","author":"Baldassarro","year":"2017","journal-title":"Dis. Model Mech."}],"container-title":["Animals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2615\/16\/19\/3109\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T09:14:20Z","timestamp":1791191660000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2615\/16\/19\/3109"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,3]]},"references-count":61,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2026,10]]}},"alternative-id":["ani16193109"],"URL":"https:\/\/doi.org\/10.3390\/ani16193109","relation":{},"ISSN":["2076-2615"],"issn-type":[{"value":"2076-2615","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,3]]}}}