{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T06:12:46Z","timestamp":1760595166973,"version":"build-2065373602"},"reference-count":23,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T00:00:00Z","timestamp":1760572800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Metastasis is the most common cause of cancer patient deaths. It is a complex process strongly influenced by the extracellular matrix (ECM). A mass spectrometry analysis comparing ECM proteins from healthy mouse lungs versus metastatic lungs has previously been performed, and the basement membrane (BM) component nidogen-1 has been identified to be one of the most downregulated ECM proteins in metastatic lungs. Here, we investigated the role of stromal cell-derived nidogen-1 in metastasis. We found that nidogen-1 is expressed by fibroblasts but not cancer cells, and nidogen-1 is downregulated in breast tumors compared to healthy mammary gland. Using the HCmel12 melanoma model, we found that loss of stromal nidogen-1 causes increased lung metastasis. Using electron microscopy, we found that nidogen-1 knockout mice have defects in the lung alveoli, such as fragmented endothelium, poorly defined BM, and enlarged interstitium. This suggests that loss of nidogen-1 may cause BM defects, which compromise its barrier function, thereby increasing the ability of cancer cells to extravasate and colonize the lungs. Our findings provide novel insight into cancer-stromal interplay and the role of nidogen-1 at the metastatic niche.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1598547","type":"journal-article","created":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T05:32:52Z","timestamp":1760592772000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Loss of nidogen-1 causes lung basement membrane defects and increased metastasis"],"prefix":"10.3389","volume":"16","author":[{"given":"Tian","family":"Xia","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kamilla W.","family":"Zornhagen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilkka","family":"Miinalainen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lilach","family":"Abramovitz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chris D.","family":"Madsen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monica","family":"Nicolau","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alejandro E.","family":"Mayorca-Guiliani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neta","family":"Erez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janine T.","family":"Erler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,16]]},"reference":[{"key":"B1","article-title":"Tumor invasion and metastases: role of the basement membrane. 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