{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T22:57:55Z","timestamp":1792277875984,"version":"4.4.0"},"reference-count":45,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2009,12,21]],"date-time":"2009-12-21T00:00:00Z","timestamp":1261353600000},"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":[[2010,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Vascular endothelial growth factor (VEGF) is one of the most important angiogenic growth factors for tumor angiogenesis. Here, we sought to explore whether RNA interference (RNAi) targeting matrix metalloproteinase\u20102 (MMP\u20102) could disrupt VEGF\u2010mediated angiogenesis in lung cancer. MMP\u20102 siRNA inhibited lung cancer cell\u2010induced tube formation of endothelial cells\n                    <jats:italic>in vitro<\/jats:italic>\n                    ; addition of recombinant human\u2010MMP\u20102 restored angiogenesis. MMP\u20102 transcriptional suppression decreased VEGF, phosphatidylinositol 3\u2010kinase (PI3K) protein levels and AKT phosphorylation in lung cancer cells. In addition, MMP\u20102 suppression decreased hypoxia inducible factor\u20101\u03b1 (HIF\u20101\u03b1), a transcription factor for VEGF, as determined by electrophoretic mobility shift assay (EMSA). We also show that MMP\u20102 suppression disrupted PI3K dependent VEGF expression; ectopic expression of myr\u2010AKT restored VEGF inhibition. Further, MMP\u20102 suppression decreased the interaction of integrin\u2010\u03b1V\u03b23 and MMP\u20102 as confirmed by immunoprecipitation analyses. Studies with either function blocking integrin\u2010\u03b1V\u03b23 antibody or MMP\u20102 specific inhibitor (ARP\u2010100) indicate that suppression of MMP\u20102 decreased integrin\u2010\u03b1V\u03b23\u2010mediated induction of PI3K\/AKT leading to decreased VEGF expression. Moreover, A549 xenograft tissue sections from mice that treated with MMP\u20102 siRNA showed reduced expression of VEGF and the angiogenic marker, factor\u2010VIII. The inhibition of tumor angiogenesis in MMP\u20102 suppressed tumor sections was associated with decreased co\u2010localization of integrin\u2010\u03b1V\u03b23 and MMP\u20102. In summary, these data provide new insights into the mechanisms underlying MMP\u20102\u2010mediated VEGF expression in lung tumor angiogenesis.\n                  <\/jats:p>","DOI":"10.1002\/ijc.25134","type":"journal-article","created":{"date-parts":[[2009,12,21]],"date-time":"2009-12-21T10:07:29Z","timestamp":1261390049000},"page":"1081-1095","source":"Crossref","is-referenced-by-count":181,"title":["MMP\u20102 alters VEGF expression\n                    <i>via<\/i>\n                    \u03b1V\u03b23 integrin\u2010mediated PI3K\/AKT signaling in A549 lung cancer cells"],"prefix":"10.1002","volume":"127","author":[{"given":"Chandramu","family":"Chetty","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sajani S.","family":"Lakka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Praveen","family":"Bhoopathi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasti S.","family":"Rao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2010,6,25]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.med.57.121304.131306"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1093"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1094"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.5-suppl_1-3"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1476-5586(03)80044-1"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2003.09.016"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-8049(96)00401-7"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2005.09.005"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2006.02.009"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1200977"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1517\/13543784.16.1.83"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-0004.1999.560302.2.x"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1023\/B:APPT.0000045801.15585.dd"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.22.20.7004-7014.2002"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1187"},{"key":"e_1_2_6_17_2","first-page":"1541","article-title":"Modulation of hypoxia\u2010inducible factor 1alpha expression by the epidermal growth factor\/phosphatidylinositol 3\u2010kinase\/PTEN\/AKT\/FRAP pathway in human prostate cancer cells: implications for tumor angiogenesis and therapeutics","volume":"60","author":"Zhong H","year":"2000","journal-title":"Cancer Res"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.30.17771"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.21.12.3995-4004.2001"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E04-12-1087"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.02-0180"},{"key":"e_1_2_6_22_2","first-page":"1048","article-title":"Reduced angiogenesis and tumor progression in gelatinase A\u2010deficient mice","volume":"58","author":"Itoh T","year":"1998","journal-title":"Cancer Res"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.03-0249"},{"key":"e_1_2_6_24_2","first-page":"1231","article-title":"Correlation of antiangiogenic and antitumor efficacy of N\u2010biphenyl sulfonyl\u2010phenylalanine hydroxiamic acid (BPHA), an orally\u2010active, selective matrix metalloproteinase inhibitor","volume":"59","author":"Maekawa R","year":"1999","journal-title":"Cancer Res"},{"key":"e_1_2_6_25_2","first-page":"8480","article-title":"Inhibition of angiogenesis and metastasis in two murine models by the matrix metalloproteinase inhibitor. 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