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However, the quantitative assessment of how individual stromal components contribute to cytokine secretion in 3D models remains poorly understood, especially when comparing tumours of different origins. The development of 16 groups of 3D spheroid cultures, encompassing stromal monocultures, two-component models (tumor + endothelium\/glia), and three-component models (tumor + endothelium + fibroblast; glioma + astrocytes + microglia), was conducted. These models represent breast cancer and glioma cell culture models. The secretion of 32 distinct cytokines was measured using xMAP technology. Induction was defined as log2FC \u2265 1 with bootstrap-estimated 95% confidence intervals. The induced cytokines were subsequently classified into two operational categories: \u201cemergent\u201d (stromal monoculture level below 3D-2) or \u201cstroma-contributing\u201d (stromal level \u2265 3D-2). In the breast cancer model, a consensus across all cell lines identified seven cytokines (HGF, IL-10, LIF, MCP-1, MCP-3, MIP-1\u03b1, and SCGF-\u03b2). Cancer-associated fibroblasts (CAFs) were associated with a broader spectrum than normal fibroblasts (28 vs. 23), exhibiting a complete overlap in their repertoire. Triple-negative breast cancer (MDA-MB-231) showed minimal secretion (7\u20138 cytokines), with decreased secretion of GM-CSF and IP-10; b-FGF levels were reduced in six of eight comparisons. In the glioma model based on U87MG cells, the addition of astrocytes (CCF-STTG1) coincided with increased secretion of 13 different cytokines, whereas microglia (HMC3) were associated with 8 cytokines. The cross-tumor intersection comprised 14 cytokines (7 chemokines, 5 growth factors, and 2 immunoregulatory cytokines), with maximal production observed for LIF, IL-8, MCP-3, MIP-1\u03b1, and IL-6. These findings indicate that the addition of stromal cells is associated with both common and tissue-specific changes in the cytokine profile, and that CAFs display a broader secretory repertoire than normal fibroblasts in this model.<\/jats:p>","DOI":"10.3390\/cells15191728","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T15:28:43Z","timestamp":1790090923000},"page":"1728","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Stromal Remodeling of the Cytokine Secretome Reveals a Chemokine Core Across Breast Cancer and Glioma 3D Cell Culture Models"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5027-6561","authenticated-orcid":false,"given":"David","family":"Sergeevichev","sequence":"first","affiliation":[{"name":"Scientific Center of Genetics and Life Sciences, Sirius University of Science and Technology, 1 Olimpiysky Avenue, Sirius (Federal Territory of Sirius), Sochi 354340, Russia"},{"name":"Meshalkin National Medical Research Center, 15, Rechkunovskaya St., Novosibirsk 630090, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1477-1118","authenticated-orcid":false,"given":"Anastasia","family":"Leonteva","sequence":"additional","affiliation":[{"name":"Scientific Center of Genetics and Life Sciences, Sirius University of Science and Technology, 1 Olimpiysky Avenue, Sirius (Federal Territory of Sirius), Sochi 354340, Russia"},{"name":"Laboratory of Biotechnology, Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Sciences, 8, Akad. Lavrentiev Ave., Novosibirsk 630090, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Alina","family":"Kazakova","sequence":"additional","affiliation":[{"name":"Scientific Center of Genetics and Life Sciences, Sirius University of Science and Technology, 1 Olimpiysky Avenue, Sirius (Federal Territory of Sirius), Sochi 354340, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"}]},{"given":"Maria","family":"Bogachek","sequence":"additional","affiliation":[{"name":"Scientific Center of Genetics and Life Sciences, Sirius University of Science and Technology, 1 Olimpiysky Avenue, Sirius (Federal Territory of Sirius), Sochi 354340, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Anna","family":"Ilyina","sequence":"additional","affiliation":[{"name":"Scientific Center of Genetics and Life Sciences, Sirius University of Science and Technology, 1 Olimpiysky Avenue, Sirius (Federal Territory of Sirius), Sochi 354340, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"given":"Vladimir","family":"Richter","sequence":"additional","affiliation":[{"name":"Laboratory of Biotechnology, Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Sciences, 8, Akad. 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