{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T06:33:47Z","timestamp":1777876427099,"version":"3.51.4"},"reference-count":84,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2019,1,1]],"date-time":"2019-01-01T00:00:00Z","timestamp":1546300800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007225","name":"Ministry of Science and Technology","doi-asserted-by":"publisher","award":["MOST 105-2320-B-468-004-MY3"],"award-info":[{"award-number":["MOST 105-2320-B-468-004-MY3"]}],"id":[{"id":"10.13039\/100007225","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007225","name":"Ministry of Science and Technology","doi-asserted-by":"publisher","award":["MOST 106-2311-B-039-002"],"award-info":[{"award-number":["MOST 106-2311-B-039-002"]}],"id":[{"id":"10.13039\/100007225","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004391","name":"China Medical University Hospital","doi-asserted-by":"publisher","award":["DMR-108-160"],"award-info":[{"award-number":["DMR-108-160"]}],"id":[{"id":"10.13039\/501100004391","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007300","name":"China Medical University","doi-asserted-by":"publisher","award":["CMU106-ASIA-07"],"award-info":[{"award-number":["CMU106-ASIA-07"]}],"id":[{"id":"10.13039\/501100007300","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007300","name":"China Medical University","doi-asserted-by":"publisher","award":["CMU107-N-14"],"award-info":[{"award-number":["CMU107-N-14"]}],"id":[{"id":"10.13039\/501100007300","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Taichung Tzu Chi Hospital","award":["TTCRD107-03"],"award-info":[{"award-number":["TTCRD107-03"]}]},{"name":"Taichung Tzu Chi Hospital","award":["TTCRD108-07"],"award-info":[{"award-number":["TTCRD108-07"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Ther Adv Med Oncol"],"published-print":{"date-parts":[[2019,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Leptin is considered a tumorigenic adipokine, suggested to promote tumorigenesis and progression in many cancers. On the other hand, intercellular adhesion molecule-1 (ICAM-1) shows altered expression in a variety of benign and malignant diseases. Histologically, ICAM-1 expression is reported as proportional to cancer stage and considered as a potential diagnosis biomarker. The altered expressions of ICAM-1 and its soluble form in malignant diseases have gained interests in recent years.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Material and methods:<\/jats:title>\n                    <jats:p>The expression of ICAM-1 and its regulatory signaling were examined by Western blot or flow cytometry. The effect of soluble ICAM-1 on osteoclast formation was investigated by tartrate-resistance acid phosphatase staining of RAW cells and tumor-induced osteolysis in vivo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>In our study, we found that leptin enhanced soluble ICAM-1 production but not surface ICAM-1 expression in lung and breast cancer cells, and this effect was regulated through leptin receptor (ObR), while silencing ObR abrogated leptin-induced soluble ICAM-1 expression. In addition, we revealed that leptin administration provoked the JAK1\/2, STAT3, FAK, ERK, and GSK3\u03b1\u03b2 signaling cascade, leading to the elevation of ICAM-1 expression. Moreover, soluble ICAM-1\u2009secreted by leptin-stimulated cancer cells synergize with the receptor activator of nuclear factor kappa-B ligand (RANKL) in inducing osteoclast formation. Soluble ICAM also enhanced tumor-induced osteolysis in vivo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>These findings suggest that soluble ICAM-1 produced under leptin treatment enhances osteoclast formation and is involved in tumor-induced osteolysis. Leptin plays an important role in physiology in health and diseases. Leptin affects immune responses that may induce inflammation and carcinogenesis. Leptin is also considered as a tumorigenic adipokine suggested to promote tumorigenesis and progression in many cancers. On the other hand, intercellular adhesion molecule-1 (ICAM-1) shows altered expression in a variety of benign and malignant diseases. Histologically, ICAM-1 expression is reported to be proportional to cancer stage and considered as a potential diagnosis biomarker. It has been reported that soluble ICAM-1 allows tumor cells to escape from immune recognition and stimulates angiogenesis and tumor growth. The altered expressions of ICAM-1 and its soluble form in malignant diseases have gained interests in recent years. In our study, we found that leptin enhanced soluble ICAM-1 production but not surface ICAM-1 expression in lung and breast cancer cells, and this effect was regulated through leptin receptor (ObR), while silencing ObR abrogated leptin-induced soluble ICAM-1 expression. In addition, we revealed that leptin administration provoked the JAK1\/2, STAT3, FAK, ERK, and GSK3\u03b1\u03b2 signaling cascade, leading to the elevation of ICAM-1 expression. Moreover, soluble ICAM-1\u2009secreted by leptin-stimulated cancer cells synergize with receptor activator of nuclear factor-kappa B ligand in inducing osteoclast formation. Soluble ICAM also enhanced tumor-induced osteolysis in vivo. These findings suggest that soluble ICAM-1 produced under leptin treatment is possibly involved in lung and breast cancer bone metastasis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/1758835919846806","type":"journal-article","created":{"date-parts":[[2019,5,14]],"date-time":"2019-05-14T07:33:03Z","timestamp":1557819183000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":20,"title":["Induction of osteoclast-like cell formation by leptin-induced soluble intercellular adhesion molecule secreted from cancer cells"],"prefix":"10.1177","volume":"11","author":[{"given":"Cheng-Fang","family":"Tsai","sequence":"first","affiliation":[{"name":"Department of Biotechnology, Asia University, Taichung, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia-Hong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen-Teng","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Surgery, China Medical University Hospital, Taichung, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pei-Chun","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics and Medical Engineering, Asia University, Taichung, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shu-Lin","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of New Drug Development, China Medical University, Taichung, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4398-7610","authenticated-orcid":false,"given":"Wei-Lan","family":"Yeh","sequence":"additional","affiliation":[{"name":"Institute of New Drug Development, China Medical University, No. 91 Hsueh-Shih Road, Taichung, 40402 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