{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:51:09Z","timestamp":1790700669419,"version":"4.1.0"},"reference-count":28,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2005,11,17]],"date-time":"2005-11-17T00:00:00Z","timestamp":1132185600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2006,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In an orthotopic murine model of head and neck cancer, combined subcutaneous and intratumoral vaccination with recombinant vaccinia virus expressing interleukin\u20102 (rvv\u2010IL\u20102) induced significant tumor regression early on therapy. However, its efficacy was restricted by recurrent tumor growth and loco\u2010regional metastases. In this study, we explored the mechanism of tumor metastasis. We compared the levels of expression of a number of molecules involved in tumor metastasis, which included transforming growth factor\u2010\u03b21 (TGF\u2010\u03b21), E\u2010cadherin, matrix metalloproteinases (MMPs): MT1\u2010MMP, MMP\u20102, MMP\u20109, their tissue inhibitors (TIMPs): TIMP\u20101\/TIMP\u20102, and pro\u2010angiogenic factors CD31, VEGF\u2010R2, and iNOS between primary and metastatic tumors by real\u2010time RT\u2010PCR and immunohistochemistry. We detected spontaneous lymph node and tongue metastasis. Metastasis was delayed in rvv\u2010IL\u20102 treated mice. Cultured tumor cells expressed negligible amount of TGF\u2010\u03b21. Untreated or metastatic tumors, on the other hand, expressed high levels of TGF\u2010\u03b21 and secreted TGF\u2010\u03b21 in the sera of tumor\u2010bearing mice. Levels of TGF\u2010\u03b21 in the sera suddenly jumped at the time when tumor metastasis started. In the metastatic tumors, levels of MT1\u2010MMP, MMP\u20102, and MMP\u20109 were significantly elevated (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001), while levels of TIMP\u20101\/TIMP\u20102 and E\u2010cadherin were decreased (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001) compared to control or primary tumors. Levels of CD31, VEGF\u2010R2, and iNOS were also significantly elevated in the metastatic lesions (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001). The concurrence of high levels of TGF\u2010\u03b21 in the sera, expression of proteins involved in metastasis and initiation of metastasis suggested possible role of TGF\u2010\u03b21 in on setting the metastatic cascade in this model. J. Cell. Biochem. \u00a9 2005 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcb.20647","type":"journal-article","created":{"date-parts":[[2005,11,17]],"date-time":"2005-11-17T17:47:10Z","timestamp":1132249630000},"page":"1036-1051","source":"Crossref","is-referenced-by-count":37,"title":["Tumor metastasis in an orthotopic murine model of head and neck cancer: Possible role of TGF\u2010beta 1 secreted by the tumor cells"],"prefix":"10.1002","volume":"97","author":[{"given":"Santanu","family":"Dasgupta","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malaya","family":"Bhattacharya\u2010Chatterjee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Bert W.","family":"O'Malley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunil K.","family":"Chatterjee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,11,17]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/87895"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/89.17.1260"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9896(199911)189:3<300::AID-PATH456>3.0.CO;2-C"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1525-0016(03)00148-5"},{"key":"e_1_2_5_6_1","first-page":"375","article-title":"Reversal of immune suppression following vaccination with recombinant vaccinia virus expressing IL\u20102 in an orthotopic murine model of head and neck squamous cell carcinoma","volume":"2","author":"Dasgupta S","year":"2004","journal-title":"Cancer Ther"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.10654"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.10593"},{"key":"e_1_2_5_9_1","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1096\/fasebj.11.12.9337152","article-title":"Latent transforming growth factor beta1 activation in situ: Quantitative and functional evidence after low\u2010dose gamma\u2010irradiation","volume":"11","author":"Ehrhart EJ","year":"1997","journal-title":"FASEB J"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.10916"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-03-2144"},{"key":"e_1_2_5_12_1","first-page":"8221","article-title":"Expression of matrix metalloproteinases in the microenvironment of spontaneous and experimental melanoma metastases reflects the requirements for tumor formation","volume":"63","author":"Hofmann UB","year":"2003","journal-title":"Cancer Res"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1204535"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.11.5883"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001622-200205000-00014"},{"key":"e_1_2_5_16_1","first-page":"1551","article-title":"Combination surgery and nonviral interleukin 2 gene therapy for head and neck cancer","volume":"5","author":"Li D","year":"1999","journal-title":"Clin Cancer Res"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.3700003"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-04-1032"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(00)00038-5"},{"key":"e_1_2_5_20_1","first-page":"151","article-title":"Activation mechanisms of matrix metalloproteinases","volume":"378","author":"Nagase H","year":"1997","journal-title":"Biol Chem"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1001\/archotol.1997.01900010022003"},{"key":"e_1_2_5_22_1","first-page":"163","article-title":"Recombinant vaccinia expressing interleukin\u20102 for cancer gene therapy","volume":"3","author":"Qin H","year":"1996","journal-title":"Cancer Gene Ther"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1006\/mthe.2001.0493"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-8049(01)00399-9"},{"key":"e_1_2_5_25_1","first-page":"775","article-title":"Vascular endothelial growth factor is a marker of tumor invasion and metastasis in squamous cell carcinomas of the head and neck","volume":"5","author":"Sauter ER","year":"1999","journal-title":"Clin Cancer Res"},{"key":"e_1_2_5_26_1","first-page":"8511","article-title":"Significance of MMP\u20102 expression in prostate cancer: An immunohistochemical study","volume":"63","author":"Trudel D","year":"2003","journal-title":"Cancer Res"},{"key":"e_1_2_5_27_1","first-page":"7435","article-title":"Inducible expression of transforming growth factor beta1 in papillomas causes rapid metastasis","volume":"61","author":"Weeks BH","year":"2001","journal-title":"Cancer Res"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1015531319087"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200215333"}],"container-title":["Journal of Cellular Biochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcb.20647","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcb.20647","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,9]],"date-time":"2023-10-09T13:13:23Z","timestamp":1696857203000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcb.20647"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,11,17]]},"references-count":28,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2006,4]]}},"alternative-id":["10.1002\/jcb.20647"],"URL":"https:\/\/doi.org\/10.1002\/jcb.20647","archive":["Portico"],"relation":{},"ISSN":["0730-2312","1097-4644"],"issn-type":[{"value":"0730-2312","type":"print"},{"value":"1097-4644","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,11,17]]}}}