{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:45:26Z","timestamp":1785422726477,"version":"3.56.0"},"reference-count":111,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003141","name":"Secretar\u00eda de Ciencia, Humanidades, Tecnolog\u00eda e Innovaci\u00f3n","doi-asserted-by":"crossref","award":["C-1597\/2025"],"award-info":[{"award-number":["C-1597\/2025"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"crossref"}]},{"award":["C-1597\/2025"],"award-info":[{"award-number":["C-1597\/2025"]}],"id":[{"id":"https:\/\/ror.org\/059ex5q34","id-type":"ROR","asserted-by":"publisher"}]},{"name":"SECIHTI","award":["712865"],"award-info":[{"award-number":["712865"]}]},{"name":"SECIHTI","award":["1035170"],"award-info":[{"award-number":["1035170"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Obesity is recognized as a risk factor for breast cancer development and progression. Adipocytes exert their oncogenic effects through complex and interconnected biological mechanisms that encompass metabolic dysfunction, chronic low-grade inflammation, and systemic endocrine alterations. Herein, we reviewed the current evidence explaining how obesity induces a state that reprograms adipose tissue and remodels the breast cancer tumor microenvironment (TME). We first discuss the systemic and local mechanisms linking obesity to inflammation and how these alterations reshape the functional organization of the mammary gland. Then, we discuss how the chronic exposure to tumor-derived signals, together with the altered metabolic state of obese adipose tissue, induces a functional reprogramming of adipocytes, giving rise to so-called cancer-associated adipocytes (CAAs), which actively contribute to tumor progression. Also, the strengths and limitations of biological models to study the crosstalk between adipocytes and tumor cells, including two-dimensional (2D) monolayers and three-dimensional (3D) cell cultures, as well as animal models, are discussed. Special emphasis is placed on 3D co-culture models, which more accurately reproduce spatial organization, direct cell\u2013cell contact, and diffusion dynamics, providing a more physiologically relevant environment for studying how obesity and inflammation reshape the TME in breast cancer. Finally, we highlight the limitations of conventional experimental models and review recent advances in 3D-based platforms, emphasizing their mechanistic insights and translational potential.<\/jats:p>","DOI":"10.3390\/cells15090761","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T17:26:18Z","timestamp":1777051578000},"page":"761","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Obesity, Inflammation, and Tumor Microenvironment in Three-Dimensional Models of Breast Cancer"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2129-9980","authenticated-orcid":false,"given":"Yarely M.","family":"Salinas-Vera","sequence":"first","affiliation":[{"name":"Posgrado en Ciencias Gen\u00f3micas, Universidad Aut\u00f3noma de la Ciudad de M\u00e9xico, Ciudad de M\u00e9xico 03100, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yussel","family":"P\u00e9rez-Navarro","sequence":"additional","affiliation":[{"name":"Posgrado en Ciencias Gen\u00f3micas, Universidad Aut\u00f3noma de la Ciudad de M\u00e9xico, Ciudad de M\u00e9xico 03100, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6941-6248","authenticated-orcid":false,"given":"Jonathan","family":"Puente-Rivera","sequence":"additional","affiliation":[{"name":"Divisi\u00f3n de Investigaci\u00f3n, Hospital Ju\u00e1rez de M\u00e9xico, Ciudad de M\u00e9xico 07760, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9212-4451","authenticated-orcid":false,"given":"Mar\u00eda Elizbeth","family":"\u00c1lvarez-S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Posgrado en Ciencias Gen\u00f3micas, Universidad Aut\u00f3noma de la Ciudad de M\u00e9xico, Ciudad de M\u00e9xico 03100, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9417-2609","authenticated-orcid":false,"given":"C\u00e9sar","family":"L\u00f3pez-Camarillo","sequence":"additional","affiliation":[{"name":"Posgrado en Ciencias Gen\u00f3micas, Universidad Aut\u00f3noma de la Ciudad de M\u00e9xico, Ciudad de M\u00e9xico 03100, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,24]]},"reference":[{"key":"ref_1","first-page":"12","article-title":"Cancer statistics, 2024","volume":"74","author":"Siegel","year":"2024","journal-title":"CA Cancer J. 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