{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:34:38Z","timestamp":1791232478558,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2011,9,16]],"date-time":"2011-09-16T00:00:00Z","timestamp":1316131200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2012,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Previously, we have demonstrated that a variety of human cancers including the ovarian cancer express IL\u201013R\u03b12, a high affinity receptor for IL\u201013. Herein, we have examined if IL\u201013 regulates invasion and metastasis of ovarian cancer through IL\u201013R\u03b12\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    in animal models of human ovarian cancer. We tested cell invasion and protease activity in IL\u201013R\u03b12\u2010overexpressing and IL\u201013R\u03b12\u2010negative ovarian tumor cell lines. IL\u201013 treatment significantly augmented both cell invasion and enzyme activities in only IL\u201013R\u03b12\u2010positive cells but not in IL\u201013R\u03b12\u2010negative cells\n                    <jats:italic>in vitro<\/jats:italic>\n                    . Mechanistically, IL\u201013 enhanced ERK1\/2, AP\u20101 and MMP activities only in IL\u201013R\u03b12\u2010positive cells but not in IL\u201013R\u03b12\u2010negative cells. In contrast, other signaling pathways such as IRS1\/2, PI3K and AKT do not seem to be involved in IL\u201013 induced signaling in ovarian cancer cell lines. Highly specific inhibitors for MMP and AP\u20101 efficiently inhibited both invasion and protease activities without impacting the basal level invasion and protease activities\n                    <jats:italic>in vitro<\/jats:italic>\n                    . In orthotopic animal model of human ovarian cancer, IL\u201013R\u03b12\u2010positive tumors metastasized to lymph nodes and peritoneum earlier than IL\u201013R\u03b12\u2010negative tumors. Interestingly, the IL\u201013R\u03b12\u2010positive tumor bearing mice died earlier than mice with IL\u201013R\u03b12\u2010negative tumor. Intraperitoneal injection of IL\u201013 further shortened survival of IL\u201013R\u03b12\u2010positive tumor bearing mice compared to IL\u201013R\u03b12\u2010negative tumor mice. IL\u201013R\u03b12\u2010positive tumors and lymph node metastasis expressed higher levels of MMPs and higher ERK1\/2 activation compared to IL\u201013R\u03b12\u2010negative tumors. Taken together, IL\u201013R\u03b12 is involved in cancer metastasis through activation of ERK\/AP\u20101 and that targeting IL\u201013R\u03b12 might not only directly kill primary tumors but also prevent cancer metastasis.\n                  <\/jats:p>","DOI":"10.1002\/ijc.26366","type":"journal-article","created":{"date-parts":[[2011,8,19]],"date-time":"2011-08-19T15:28:28Z","timestamp":1313767708000},"page":"344-356","source":"Crossref","is-referenced-by-count":123,"title":["IL\u201013 regulates cancer invasion and metastasis through IL\u201013R\u03b12\n                    <i>via<\/i>\n                    ERK\/AP\u20101 pathway in mouse model of human ovarian cancer"],"prefix":"10.1002","volume":"131","author":[{"given":"Toshio","family":"Fujisawa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bharat H.","family":"Joshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raj K.","family":"Puri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,9,16]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.20073"},{"key":"e_1_2_5_3_2","first-page":"609","article-title":"Ovarian cancer: an overview","volume":"80","author":"Roett MA","year":"2009","journal-title":"Am Fam 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