{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T23:04:11Z","timestamp":1793142251858,"version":"4.5.0"},"reference-count":107,"publisher":"American Society for Clinical Investigation","issue":"9","license":[{"start":{"date-parts":[[2024,5,8]],"date-time":"2024-05-08T00:00:00Z","timestamp":1715126400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,5,8]]},"abstract":"<jats:p>\n                    Lung cancer is the leading cause of cancer-related deaths in the world, and non\u2013small cell lung cancer (NSCLC) is the most common subset. We previously found that infiltration of tumor inflammatory monocytes (TIMs) into lung squamous carcinoma (LUSC) tumors is associated with increased metastases and poor survival. To further understand how TIMs promote metastases, we compared RNA-Seq profiles of TIMs from several LUSC metastatic models with inflammatory monocytes (IMs) of non\u2013tumor-bearing controls. We identified\n                    <jats:italic>Spon1<\/jats:italic>\n                    as upregulated in TIMs and found that\n                    <jats:italic>Spon1<\/jats:italic>\n                    expression in LUSC tumors corresponded with poor survival and enrichment of collagen extracellular matrix signatures. We observed SPON1\n                    <jats:sup>+<\/jats:sup>\n                    TIMs mediate their effects directly through LRP8 on NSCLC cells, which resulted in TGF-\u03b21 activation and robust production of fibrillar collagens. Using several orthogonal approaches, we demonstrated that SPON1\n                    <jats:sup>+<\/jats:sup>\n                    TIMs were sufficient to promote NSCLC metastases. Additionally, we found that\n                    <jats:italic>Spon1<\/jats:italic>\n                    loss in the host, or\n                    <jats:italic>Lrp8<\/jats:italic>\n                    loss in cancer cells, resulted in a significant decrease of both high-density collagen matrices and metastases. Finally, we confirmed the relevance of the SPON1\/LRP8\/TGF-\u03b21 axis with collagen production and survival in patients with NSCLC. Taken together, our study describes how SPON1\n                    <jats:sup>+<\/jats:sup>\n                    TIMs promote collagen remodeling and NSCLC metastases through an LRP8\/TGF-\u03b21 signaling axis.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.168792","type":"journal-article","created":{"date-parts":[[2024,5,7]],"date-time":"2024-05-07T14:00:34Z","timestamp":1715090434000},"source":"Crossref","is-referenced-by-count":19,"title":["Spon1+ inflammatory monocytes promote collagen remodeling and lung cancer metastasis through lipoprotein receptor 8 signaling"],"prefix":"10.1172","volume":"9","author":[{"given":"Kristina M.","family":"Whately","sequence":"first","affiliation":[{"name":"UNC Lineberger Comprehensive Cancer Center and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nisitha","family":"Sengottuvel","sequence":"additional","affiliation":[{"name":"UNC Lineberger Comprehensive Cancer Center and"},{"name":"Department of Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lincy","family":"Edatt","sequence":"additional","affiliation":[{"name":"UNC Lineberger Comprehensive Cancer Center and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonal","family":"Srivastava","sequence":"additional","affiliation":[{"name":"Department of Tumor Microenvironment and Metastasis, H. 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