{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:01:17Z","timestamp":1785427277686,"version":"3.56.0"},"reference-count":27,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002322","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["200177\/2022-2"],"award-info":[{"award-number":["200177\/2022-2"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"award":["200177\/2022-2"],"award-info":[{"award-number":["200177\/2022-2"]}],"id":[{"id":"https:\/\/ror.org\/03swz6y49","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Veterinary Sciences"],"abstract":"<jats:p>Canine mixed-type mammary carcinomas (CMTs) exhibit remarkable histological and structural heterogeneity, sharing some biological similarities with human breast cancer and supporting their relevance as models in comparative oncology. These tumors frequently contain regions of malignant epithelial cells, areas of mesenchymal differentiation, and ossified tissue, reflecting their complex histological organization. In this exploratory pilot study, we performed MRM-based spatial lipidomic analysis of distinct tumor regions; namely the margin, middle (epithelial\/myoepithelial-rich), and central ossified areas. Our region-resolved lipidomic analysis revealed distinct lipidomic signatures across regions, with significant alterations in phosphatidylcholines, phosphatidylethanolamines, sphingomyelins, triacylglycerides, and free fatty acids distribution. The central ossified area showed enrichment in structural lipids and ceramides, while the tumor margin demonstrated enrichment of ether lipids, which may reflect differences in tissue composition and local metabolic environments. By characterizing region-specific lipid profiles, this study provides insights into metabolic heterogeneity within a canine mixed mammary carcinoma. These findings highlight the potential of spatial lipidomics for investigating intratumoral metabolic heterogeneity and provide preliminary data to support future studies in comparative oncology involving canine and human mammary tumors.<\/jats:p>","DOI":"10.3390\/vetsci13070689","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T06:49:36Z","timestamp":1784184576000},"page":"689","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploratory Spatial Lipidomic Profiling Reveals Regional Metabolic Heterogeneity in a Canine Mixed Mammary Carcinoma"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9736-8113","authenticated-orcid":false,"given":"M\u00f4nica","family":"Duarte da Silva","sequence":"first","affiliation":[{"name":"Graduate Program in Anatomy of Domestic and Wild Animals, Faculty of Veterinary Medicine and Animal Science, University of S\u00e3o Paulo (FMVZ\/USP), S\u00e3o Paulo 05508-270, SP, Brazil"},{"name":"Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina Ramires","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Bindley Bioscience Center, Purdue University, West Lafayette, IN 47907, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8733-4932","authenticated-orcid":false,"given":"Hianka Jasmyne","family":"Costa de Carvalho","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5035-876X","authenticated-orcid":false,"given":"Sandra Maria","family":"Barbalho","sequence":"additional","affiliation":[{"name":"Graduate Program in Structural and Functional Interactions in Rehabilitation, School of Medicine, Universidade de Mar\u00edlia (UNIMAR), Mar\u00edlia 17525-902, SP, Brazil"},{"name":"Laboratory for Systematic Investigations of Diseases, Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Mar\u00edlia (UNIMAR), Mar\u00edlia 17525-902, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5240-6959","authenticated-orcid":false,"given":"Rodrigo da Silva Nunes","family":"Barreto","sequence":"additional","affiliation":[{"name":"RB Laboratory, College of Agricultural and Veterinary Sciences, S\u00e3o Paulo State University (UNESP), Jaboticabal 17525-902, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4143-4302","authenticated-orcid":false,"given":"Rosa","family":"Direito","sequence":"additional","affiliation":[{"name":"Laboratory of Systems Integration Pharmacology, Clinical and Regulatory Science, Research Institute for Medicines, Universidade de Lisboa (iMed.ULisboa), 1649-003 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4979-115X","authenticated-orcid":false,"given":"Maria Ang\u00e9lica","family":"Miglino","sequence":"additional","affiliation":[{"name":"Graduate Program in Structural and Functional Interactions in Rehabilitation, School of Medicine, Universidade de Mar\u00edlia (UNIMAR), Mar\u00edlia 17525-902, SP, Brazil"},{"name":"Graduate Program in Animal Health, Production and Environment, School of Veterinary Medicine, Universidade de Mar\u00edlia (UNIMAR), Mar\u00edlia 17525-902, SP, Brazil"},{"name":"Department of Animal Anatomy, School of Veterinary Medicine, Universidade de Mar\u00edlia (UNIMAR), Mar\u00edlia 17525-902, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,15]]},"reference":[{"key":"ref_1","first-page":"38","article-title":"Consensus for the diagnosis, prognosis and treatment of canine mammary tumors-2013","volume":"7","author":"Cassali","year":"2014","journal-title":"Braz. J. Vet. Pathol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Carvalho, P.T., Niza-Ribeiro, J., Amorim, I., Queiroga, F., Severo, M., Ribeiro, A.I., and Pinello, K. (2023). Comparative epidemiological study of breast cancer in humans and canine mammary tumors: Insights from Portugal. Front. Vet. Sci., 10.","DOI":"10.3389\/fvets.2023.1271097"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1111\/j.1748-5827.2000.tb03203.x","article-title":"Factors influencing the incidence and prognosis of canine mammary tumours","volume":"41","author":"Nieto","year":"2000","journal-title":"J. Small Anim. Pract."},{"key":"ref_4","first-page":"8195","article-title":"Canine mammary tumors as a model for human disease","volume":"15","author":"Abdelmegeed","year":"2018","journal-title":"Oncol. Lett."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Gray, M., Meehan, J., Mart\u00ednez-P\u00e9rez, C., Kay, C., Turnbull, A.K., Morrison, L.R., Pang, L.Y., and Argyle, D. (2020). Naturally-occurring canine mammary tumors as a translational model for human breast cancer. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.00617"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"102050","DOI":"10.1016\/j.tice.2023.102050","article-title":"The extracellular matrix protein pattern in the canine neoplastic mammary gland","volume":"82","author":"Barreto","year":"2023","journal-title":"Tissue Cell"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"105048","DOI":"10.1016\/j.chemphyslip.2021.105048","article-title":"Multiple reaction monitoring profiling (MRM profiling): Small molecule exploratory analysis guided by chemical functionality","volume":"235","author":"Xie","year":"2021","journal-title":"Chem. Phys. Lipids"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e189","DOI":"10.1038\/oncsis.2015.49","article-title":"Lipid metabolic reprogramming in cancer cells","volume":"5","author":"Vasseur","year":"2016","journal-title":"Oncogenesis"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.cmet.2022.01.007","article-title":"The hallmarks of cancer metabolism: Still emerging","volume":"34","author":"Pavlova","year":"2022","journal-title":"Cell Metab."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1139\/y59-099","article-title":"A rapid method of total lipid extraction and purification","volume":"37","author":"Bligh","year":"1959","journal-title":"Can. J. Biochem. Physiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3fc1f5fe.1972c438","DOI":"10.7171\/3fc1f5fe.1972c438","article-title":"Step-by-step approach to build multiple reaction monitoring (MRM) profiling instrument acquisition methods for class-based lipid exploratory analysis by mass spectrometry","volume":"34","author":"Reis","year":"2023","journal-title":"J. Biomol. Tech."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1038\/s41416-019-0650-z","article-title":"Reprogramming of fatty acid metabolism in cancer","volume":"122","author":"Koundouros","year":"2020","journal-title":"Br. J. Cancer"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1186\/s13045-023-01498-2","article-title":"Lipid metabolic reprogramming in tumor microenvironment: From mechanisms to therapeutics","volume":"16","author":"Jin","year":"2023","journal-title":"J. Hematol. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Pal, P., Atilla-Gokcumen, G.E., and Frasor, J. (2022). Emerging roles of ceramides in breast cancer biology and therapy. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231911178"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Corsetto, P.A., Zava, S., Rizzo, A.M., and Colombo, I. (2023). The critical impact of sphingolipid metabolism in breast cancer progression and drug response. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24032107"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"15117","DOI":"10.1038\/s41598-024-65821-8","article-title":"Impending role of inflammatory markers and their specificity and sensitivity in breast cancer patients","volume":"14","author":"Malik","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_17","first-page":"3674","article-title":"Increased apoptosis is associated with robust immune cell infiltration and cytolytic activity in breast cancer","volume":"11","author":"Murthy","year":"2021","journal-title":"Am. J. Cancer Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1093\/jnci\/80.3.188","article-title":"Polyunsaturated fatty acid-induced cytotoxicity against tumor cells and its relationship to lipid peroxidation","volume":"80","author":"Ells","year":"1988","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Chu, I., Chen, Y.-C., Lai, R.-Y., Chan, J.-F., Lee, Y.-H., Balazova, M., and Hsu, Y.-H. (2022). Phosphatidylglycerol supplementation alters mitochondrial morphology and cardiolipin composition. Membranes, 12.","DOI":"10.3390\/membranes12040383"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1186\/s12964-024-01626-6","article-title":"Signaling controversy and future therapeutical perspectives of targeting sphingolipid network in cancer immune editing and resistance to tumor necrosis factor-\u03b1 immunotherapy","volume":"22","author":"Sukocheva","year":"2024","journal-title":"Cell Commun. Signal."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Li, R.Z., Wang, X.R., Wang, J., Xie, C., Wang, X.X., Pan, H.D., Meng, W.Y., Liang, T.L., Li, J.X., and Yan, P.Y. (2022). The key role of sphingolipid metabolism in cancer: New therapeutic targets, diagnostic and prognostic values, and anti-tumor immunotherapy resistance. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.941643"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/bs.ircmb.2015.10.001","article-title":"Phosphatidylethanolamine metabolism in health and disease","volume":"321","author":"Calzada","year":"2016","journal-title":"Int. Rev. Cell Mol. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"101529","DOI":"10.1016\/j.molmet.2022.101529","article-title":"New dawn for cancer cell death: Emerging role of lipid metabolism","volume":"63","author":"Zhang","year":"2022","journal-title":"Mol. Metab."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"14912","DOI":"10.1073\/pnas.1310894110","article-title":"Ether lipid generating enzyme AGPS alters the balance of structural and signaling lipids to fuel cancer pathogenicity","volume":"110","author":"Benjamin","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1038\/s41586-020-2732-8","article-title":"Plasticity of ether lipids promotes ferroptosis susceptibility and evasion","volume":"585","author":"Zou","year":"2020","journal-title":"Nature"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1186\/s12944-025-02791-4","article-title":"From biosynthesis to function: The roles of ether lipids in cancer development and treatment","volume":"24","author":"Hu","year":"2025","journal-title":"Lipids Health Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.1038\/s41467-026-68547-5","article-title":"Ether lipids influence cancer cell fate by modulating iron uptake","volume":"17","author":"Mansell","year":"2026","journal-title":"Nat. Commun."}],"container-title":["Veterinary Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2306-7381\/13\/7\/689\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T07:37:14Z","timestamp":1784187434000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2306-7381\/13\/7\/689"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,15]]},"references-count":27,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["vetsci13070689"],"URL":"https:\/\/doi.org\/10.3390\/vetsci13070689","relation":{},"ISSN":["2306-7381"],"issn-type":[{"value":"2306-7381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,15]]}}}