{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T17:28:14Z","timestamp":1790270894951,"version":"4.1.0"},"reference-count":43,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,9,8]],"date-time":"2014-09-08T00:00:00Z","timestamp":1410134400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100005984","name":"The Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (Needham, MA, USA)","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100005984","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2015,3,15]]},"abstract":"<jats:p>\n                    Brain metastases occur frequently in melanoma patients with advanced disease whereby the prognosis is dismal. The underlying mechanisms of melanoma brain metastasis development are not well understood. Identification of molecular determinants regulating melanoma brain metastasis would advance the development of prevention and therapy strategies for this disease. Gene expression profiles of cutaneous and brain\u2010metastasizing melanoma variants from three xenograft tumor models established in our laboratory revealed that expression of tight junction component CLDN1 was lower in the brain\u2010metastasizing variants than in cutaneous variants from the same melanoma. The objective of our study was to determine the significance of CLDN1 downregulation\/loss in metastatic melanoma and its role in melanoma brain metastasis. An immunohistochemical analysis of human cells of the melanocyte lineage indicated a significant CLDN1 downregulation in metastatic melanomas. Transduction of melanoma brain metastatic cells expressing low levels of CLDN1 with a\n                    <jats:italic>CLDN1<\/jats:italic>\n                    retrovirus suppressed their metastatic phenotype. CLDN1\u2010overexpressing melanoma cells expressed a lower ability to migrate and adhere to extracellular matrix, reduced tumor aggressiveness in nude mice and, most importantly, eliminated the formation of micrometastases in the brain. In sharp contrast, the ability of the CLDN1\u2010overexpressing cells to form lung micrometastases was not impaired. CLDN1\u2010mediated interactions between these cells and brain endothelial cells constitute the mechanism underlying these results. Taken together, we demonstrated that downregulation or loss of CLDN1 supports the formation of melanoma brain metastasis, and that CLDN1 expression could be a useful prognostic predictor for melanoma patients with a high risk of brain metastasis.\n                  <\/jats:p>","DOI":"10.1002\/ijc.29090","type":"journal-article","created":{"date-parts":[[2014,7,21]],"date-time":"2014-07-21T05:43:33Z","timestamp":1405921413000},"page":"1296-1307","source":"Crossref","is-referenced-by-count":48,"title":["The metastatic microenvironment: Claudin\u20101 suppresses the malignant phenotype of melanoma brain metastasis"],"prefix":"10.1002","volume":"136","author":[{"given":"Sivan","family":"Izraely","sequence":"first","affiliation":[{"name":"Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences Tel Aviv University Tel Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orit","family":"Sagi\u2010Assif","sequence":"additional","affiliation":[{"name":"Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences Tel Aviv University Tel Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anat","family":"Klein","sequence":"additional","affiliation":[{"name":"Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences Tel Aviv University Tel Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsipi","family":"Meshel","sequence":"additional","affiliation":[{"name":"Department of Cell Research and Immunology, George S. 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Wise Faculty of Life Sciences Tel Aviv University Tel Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor G.","family":"Prieto","sequence":"additional","affiliation":[{"name":"Department of Pathology The University of Texas M.D. Anderson Cancer Center Houston TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menashe","family":"Bar\u2010Eli","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology The University of Texas MD Anderson Cancer Center Houston TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Pirker","sequence":"additional","affiliation":[{"name":"Institute of Cancer Research, Department of Medicine I Medical University Vienna Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter","family":"Berger","sequence":"additional","affiliation":[{"name":"Institute of Cancer Research, Department of Medicine I Medical University Vienna Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Nahmias","sequence":"additional","affiliation":[{"name":"Inserm, U1016, Institut Cochin Paris France"},{"name":"Cnrs, UMR8104 Paris France"},{"name":"University Paris Descartes UMR\u2010S 1016, Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre\u2010Olivier","family":"Couraud","sequence":"additional","affiliation":[{"name":"Inserm, U1016, Institut Cochin Paris France"},{"name":"Cnrs, UMR8104 Paris France"},{"name":"University Paris Descartes UMR\u2010S 1016, Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dave S.B.","family":"Hoon","sequence":"additional","affiliation":[{"name":"Department of Molecular Oncology John Wayne Cancer Institute, Saint John's Health Center Santa Monica CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isaac P.","family":"Witz","sequence":"additional","affiliation":[{"name":"Department of Cell Research and Immunology, George S. 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