{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T18:17:12Z","timestamp":1780510632604,"version":"3.54.1"},"reference-count":74,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T00:00:00Z","timestamp":1768953600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"National Cancer Institute","award":["F31CA210694"],"award-info":[{"award-number":["F31CA210694"]}]},{"DOI":"10.13039\/501100004543","name":"China Scholarship Council","doi-asserted-by":"crossref","award":["201706940004"],"award-info":[{"award-number":["201706940004"]}],"id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Tissue Engineering Part A"],"abstract":"<jats:p>\n                    Biological materials composed of extracellular matrix (ECM) or its components have been successfully used for tissue repair and reconstruction. Preclinical studies, along with a cohort study following stage T1A esophageal adenocarcinoma (EAC) resection, have shown that ECM biomaterials can restore esophageal mucosa and submucosa without cancer recurrence. However, the molecular mechanisms underlying these effects remain largely unexplored. The present study investigates the\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    effects of ECM degradation products from nonmalignant esophageal (eECM) and urinary bladder (ubECM) sources on EAC cell proliferation, migration, and associated signaling pathways. Both eECM and ubECM significantly inhibited OE33 cell proliferation, with eECM exhibiting a stronger effect\u2014reducing proliferation to 25% at 24 h and 7% at 72 h compared with pepsin control (\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    &lt; 0.001). A high-throughput cell surface marker screen followed by gene and protein expression analysis revealed that both ECM sources downregulated CD164 and CXCR4, reducing CXCR4 protein levels by approximately 50% (\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    = 0.006 for eECM,\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    = 0.007 for ubECM). Notably, only eECM significantly suppressed OE33 cell migration (\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2264 0.0001) and downregulated bone morphogenetic protein 4\n                    <jats:italic toggle=\"yes\">BMP4<\/jats:italic>\n                    expression, along with its downstream targets pSMAD1\/5\/8,\n                    <jats:italic toggle=\"yes\">ID2<\/jats:italic>\n                    , and\n                    <jats:italic toggle=\"yes\">SNAI2<\/jats:italic>\n                    , thereby reducing epithelial\u2013mesenchymal transition. These findings support the concept that biochemical cues from nonmalignant ECM modulate neoplastic cell behavior. Given the involvement of PI3K-Akt and BMP4 signaling in EAC progression, ECM-based strategies may warrant further investigation as potential therapeutic approaches following esophageal cancer resection.\n                  <\/jats:p>","DOI":"10.1177\/19373341251398055","type":"journal-article","created":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T14:35:29Z","timestamp":1764858929000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Extracellular Matrix Degradation Products Inhibit Esophageal Cancer Cell Proliferation and Migration"],"prefix":"10.1177","author":[{"given":"Xue","family":"Li","sequence":"first","affiliation":[{"name":"McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."},{"name":"School of Medical Laboratory, Tianjin Medical University, Tianjin, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela J.","family":"Romero","sequence":"additional","affiliation":[{"name":"McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."},{"name":"Department of Surgery, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsey T.","family":"Saldin","sequence":"additional","affiliation":[{"name":"McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."},{"name":"Department of Surgery, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."},{"name":"Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhang","sequence":"additional","affiliation":[{"name":"McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina M.","family":"Quijano","sequence":"additional","affiliation":[{"name":"McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera S.","family":"Donnenberg","sequence":"additional","affiliation":[{"name":"McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."},{"name":"Department of Cardiothoracic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA."},{"name":"UPMC Hillman Cancer Centers, Pittsburgh, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen F.","family":"Badylak","sequence":"additional","affiliation":[{"name":"McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."},{"name":"Department of Surgery, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."},{"name":"Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, 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