{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T15:58:06Z","timestamp":1778428686029,"version":"3.51.4"},"reference-count":42,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2012,5,30]],"date-time":"2012-05-30T00:00:00Z","timestamp":1338336000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100012553","name":"Chang Gung Memorial Hospital","doi-asserted-by":"crossref","award":["CMRPG870031"],"award-info":[{"award-number":["CMRPG870031"]}],"id":[{"id":"10.13039\/100012553","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2013,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Expression of toll\u2010like receptor\u20104 (TLR4) on tumor cells is known to mediate innate immune responses that influence tumor cell growth and migration. This study aimed to characterize TLR4 expression and elucidate its functional significance in human hepatoblastoma (HB) cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Procedure<\/jats:title><jats:p>Immunohistochemistry (IHC) was used to determine TLR4 expression level and its distribution pattern in HB liver tissues. Transcripts of tumor necrosis factor (TNF)\u2010\u03b1, interleukin (IL)\u20108, matrix metalloproteinase (MMP)\u20102, MMP\u201013, tissue inhibitor of metalloproteinases (TIMP)\u20101, and TIMP\u20102 in HB HepG2 cells with lipopolysacharide (LPS) treatment were measured by quantitative PCR. Soluble cytokines and peptides in conditioned media were measured by ELISA. MMP\u20102 activity was determined by using gelatin zymography. Cell motility and invasiveness was determined using wound healing migration and Matrigel invasion assays, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>TLR4 IHC staining demonstrated that TLR4 overexpression in HB liver tissues dramatically vanished after chemotherapy. In vitro study using an HB cell line, HepG2, showed that TLR4 agonist, LPS, significantly decreased transcripts of <jats:italic>IL\u20108<\/jats:italic> and <jats:italic>TNF\u2010\u03b1<\/jats:italic>, but did not affect <jats:italic>MMP\u201013<\/jats:italic> mRNA level. By contrast, LPS only down\u2010regulated IL\u20108 production and MMP\u20102 gelatinolytic activity. The latter might be in part due to the increased levels of MMP\u20102\/TIMP\u20102 complex in conditioned media, thus leading to the decreased motility and invasiveness of HepG2 cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>HB cells overexpress TLR4, whereas TLR4 agonistic treatment inhibits migration and invasion of HB HepG2 cells. These findings suggest that TLR4 signaling pathway is a potential therapeutic target for control of HB tumor progression. Pediatr Blood Cancer 2013;60:248\u2013253. \u00a9 2012 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.24211","type":"journal-article","created":{"date-parts":[[2012,5,30]],"date-time":"2012-05-30T14:09:17Z","timestamp":1338386957000},"page":"248-253","source":"Crossref","is-referenced-by-count":10,"title":["Toll\u2010like receptor\u20104 agonist inhibits motility and invasion of hepatoblastoma HepG2 cells in 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