title: Toll-like receptor 4 prompts human breast cancer cells invasiveness via lipopolysaccharide stimulation and is overexpressed in patients with lymph node metastasis.
abstract: Toll-like receptor (TLR)4-mediated signaling has been implicated in tumor cell invasion, survival, and metastasis in a variety of cancers. This study investigated the expression and biological role of TLR4 in human breast cancer metastasis. MCF-7 and MDA-MB-231 are human breast cancer cell lines with low and high metastatic potential, respectively. Using lipopolysaccharide (LPS) to stimulate MCF-7 and MDA-MB-231 cells, expression of TLR4 mRNA and protein increased compared with that in control cells. TLR4 activation notably up-regulated expression of matrix metalloproteinase (MMP)-2, MMP-9 and vascular endothelial growth factor(VEGF) mRNA and their secretion in the supernatants of both cell lines. LPS enhanced invasion of MDA-MB-231 cells by transwell assay and MCF-7 cells by wound healing assay. LPS triggered increased expression of TLR4 downstream signaling pathway protein myeloid differentiation factor 88(MyD88) and resulted in interleukin (IL)-6 and IL-10 higher production by human breast cancer cells. Stimulation of TLR4 with LPS promoted tumorigenesis and formed metastatic lesions in liver of nude mice. Moreover, expression of TLR4 and MyD88 as well as invasiveness and migration of the cells could be blocked by TLR4 antagonist. Combined with clinicopathological parameters, TLR4 was overexpressed in human breast cancer tissue and correlated with lymph node metastasis. These findings indicated that TLR4 may participate in the progression and metastasis of human breast cancer and provide a new therapeutic target.
authors.affiliation: Department of Clinical Laboratory, The Second affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Oncology, The Second affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Clinical Laboratory, The Second affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Pathology, The Second affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
authors.forename: Longjiang
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Clinical Laboratory, The Second affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: He
authors.affiliation: Department of Clinical Laboratory, The Second affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
authors.forename: Huiyan
authors.initials: H
authors.lastname: Wen
authors.affiliation: Department of Clinical Laboratory, The Second affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Clinical Laboratory, The Second affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
authors.forename: Honghong
authors.initials: H
authors.lastname: Su
authors.affiliation: Department of Clinical Laboratory, The Second affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
authors.forename: Xueming
authors.initials: X
authors.lastname: Zhu
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D063646:Carcinogenesis / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis / Q000235:genetics / Q000473:pathology; D061986:MCF-7 Cells; D051379:Mice; D053594:Myeloid Differentiation Factor 88 / Q000096:biosynthesis* / Q000235:genetics; D009361:Neoplasm Invasiveness / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis; D015398:Signal Transduction / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D008070:Lipopolysaccharides; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D012333:RNA, Messenger; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4