{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T03:37:08Z","timestamp":1772163428433,"version":"3.50.1"},"reference-count":46,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T00:00:00Z","timestamp":1693353600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The spread of breast cancer to distant sites is the major cause of death in breast cancer patients. Increasing evidence supports the role of the tumor microenvironment (TME) in breast cancers, and its pathologic assessment has become a diagnostic and therapeutic tool. In the TME, a bidirectional interplay between tumor and stromal cells occurs, both at the primary and metastatic site. Hundreds of molecules, including cytokines, chemokines, and growth factors, contribute to this fine interaction to promote tumor spreading. Here, we investigated the effects of Rimonabant and Cannabidiol, known for their antitumor activity, on reprogramming the breast TME. Both compounds directly affect the activity of several pathways involved in breast cancer progression. To mimic tumor\u2013stroma interactions during breast-to-lung metastasis, we investigated the effect of the compounds on growth factor secretion from metastatic breast cancer cells and normal and activated lung fibroblasts. In this setting, we demonstrated the anti-metastatic potential of the two compounds, and the membrane array analyses highlighted their ability to alter the release of factors involved in the autocrine and paracrine regulation of tumor proliferation, angiogenesis, and immune reprogramming. The results enforce the antitumor potential of Rimonabant and Cannabidiol, providing a novel potential tool for breast cancer TME management.<\/jats:p>","DOI":"10.3390\/ijms241713427","type":"journal-article","created":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T09:44:46Z","timestamp":1693388686000},"page":"13427","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Rimonabant and Cannabidiol Rewrite the Interactions between Breast Cancer Cells and Tumor Microenvironment"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7066-174X","authenticated-orcid":false,"given":"Maria Chiara","family":"Proto","sequence":"first","affiliation":[{"name":"Department of Pharmacy, University of Salerno, 84084 Fisciano, SA, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0703-7231","authenticated-orcid":false,"given":"Donatella","family":"Fiore","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Salerno, 84084 Fisciano, SA, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maurizio","family":"Bifulco","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnologies, University of Naples \u201cFederico II\u201d, 80131 Naples, NA, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0576-2955","authenticated-orcid":false,"given":"Patrizia","family":"Gazzerro","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Salerno, 84084 Fisciano, SA, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1186\/s13578-020-00453-9","article-title":"Critical steps to tumor metastasis: Alterations of tumor microenvironment and extracellular matrix in the formation of pre-metastatic and metastatic niche","volume":"10","author":"Zhuyan","year":"2020","journal-title":"Cell Biosci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/978-3-030-37184-5_2","article-title":"Fibroblasts in the Tumor Microenvironment","volume":"1234","author":"Truffi","year":"2020","journal-title":"Adv. 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