{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T16:00:22Z","timestamp":1778428822191,"version":"3.51.4"},"reference-count":117,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T00:00:00Z","timestamp":1748390400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008571","name":"Southern Illinois University School of Medicine","doi-asserted-by":"publisher","award":["NIH\/NCI R15CA283669-01"],"award-info":[{"award-number":["NIH\/NCI R15CA283669-01"]}],"id":[{"id":"10.13039\/100008571","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Simmons Cancer Institute of SIU-SOM","award":["NIH\/NCI R15CA283669-01"],"award-info":[{"award-number":["NIH\/NCI R15CA283669-01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Bone marrow (BM)-derived myeloid\u2013lymphatic endothelial cell progenitors (M-LECPs) promote formation of tumor lymphatics that are responsible for metastasis to lymph nodes. The regenerative capacity of BM progenitors to other lineages is mediated through cell fusion, a process that delivers a pro-mitotic message directly to division-restricted cells. This suggested that M-LECPs might use a similar mechanism to induce division of lymphatic endothelial cells (LECs). Methods: To test this hypothesis, we determined expression of fusogenic markers in M-LECP produced in vitro and recruited to human or mouse tumors in vivo as well as quantified their fusion with LECs in both settings. Fusion in vivo was determined in female chimera mice grafted with male BM that have been implanted with MDA-MB-231 or EMT6 breast tumors. Co-staining for Y-chromosome and LEC-specific markers allowed us to quantify tumor lymphatic vessels fused with BM progenitors. Results: We found that both tumor-recruited and in-vitro-produced M-LECPs expressed multiple fusogenic regulators and possessed a significant fusogenic activity towards cultured and vessel-lining LECs. Y-chromosomes, a marker of fusion, were detected in nearly half of tumor lymphatics and were associated with mitotic division, vessel formation, and node metastasis. Both in vitro and in vivo assays showed dependency of fusion on Th2 and Toll-like receptor-4 (TLR4) pathways. Conclusions: This novel mechanism of tumor lymphatic formation triggered by fusion with BM myeloid\u2013lymphatic progenitors suggests a variety of new targets for inhibition of metastatic spread.<\/jats:p>","DOI":"10.3390\/cancers17111804","type":"journal-article","created":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T10:21:13Z","timestamp":1748427673000},"page":"1804","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Bone Marrow Myeloid\u2013Lymphatic Progenitors Expand Tumor Lymphatic Vasculature Through Cell Fusion"],"prefix":"10.3390","volume":"17","author":[{"given":"Shaswati","family":"Athaiya","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology, Immunology, and Cell Biology, Southern Illinois University School of Medicine, Springfield, IL 62794, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Volk-Draper","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Immunology, and Cell Biology, Southern Illinois University School of Medicine, Springfield, IL 62794, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7184-316X","authenticated-orcid":false,"given":"Emma","family":"Cox","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Immunology, and Cell Biology, Southern Illinois University School of Medicine, Springfield, IL 62794, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathy","family":"Robinson","sequence":"additional","affiliation":[{"name":"Simmons Cancer Institute at SIU School of Medicine, Springfield, IL 62702, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3085-8003","authenticated-orcid":false,"given":"Natalya","family":"Zinkevich","sequence":"additional","affiliation":[{"name":"College of Health, Science, and Technology, School of Integrated Sciences, Sustainability, and Public Health, University of Springfield, Springfield, IL 62703, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3958-6099","authenticated-orcid":false,"given":"Sophia","family":"Ran","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Immunology, and Cell Biology, Southern Illinois University School of Medicine, Springfield, IL 62794, USA"},{"name":"Simmons Cancer Institute at SIU School of Medicine, Springfield, IL 62702, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1002\/wsbm.1201","article-title":"Lymphatic vessels in health and disease","volume":"5","author":"Kesler","year":"2013","journal-title":"Wiley. 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