Toll-like receptor 4 prompts human breast cancer cells invasiveness via lipopolysaccharide stimulation and is overexpressed in patients with lymph node metastasis

• Published in: PloS one 2014-10, Vol.9 (10), p.e109980
• Main Authors: Yang, Huan, Wang, Bo, Wang, Tao, Xu, Longjiang, He, Chunyan, Wen, Huiyan, Yan, Jie, Su, Honghong, Zhu, Xueming
• Format: Article
• Language: English
• Subjects: Animals; Biology and Life Sciences; Biotechnology; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Cancer; Cancer cells; Cancer metastasis; Cancer therapies; Carcinogenesis - genetics; Cell culture; Cell migration; Cell Proliferation - drug effects; Cell survival; Colorectal cancer; Comparative analysis; Female; Gelatinase B; Gene expression; Gene Expression Regulation, Neoplastic - drug effects; Health aspects; Humans; Immune system; Interleukin; Interleukin 10; Invasiveness; Laboratories; Lesions; Ligands; Lipopolysaccharides; Lipopolysaccharides - administration & dosage; Liver; Lymph; Lymph nodes; Lymph Nodes - pathology; Lymphatic Metastasis - genetics; Lymphatic Metastasis - pathology; Matrix metalloproteinase; MCF-7 Cells; Medical prognosis; Medical research; Medicine and Health Sciences; Metalloproteinase; Metastases; Metastasis; Mice; Mitogens; mRNA; MyD88 protein; Myeloid Differentiation Factor 88 - biosynthesis; Myeloid Differentiation Factor 88 - genetics; Neoplasm Invasiveness - genetics; Penicillin; Proteins; RNA; RNA, Messenger - biosynthesis; Signal transduction; Signal Transduction - genetics; Signaling; Stimulation; Systematic review; Therapeutic applications; TLR4 protein; Toll-Like Receptor 4 - biosynthesis; Toll-Like Receptor 4 - genetics; Toll-like receptors; Tumor cell lines; Tumorigenesis; Vascular endothelial growth factor; Wound healing
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0109980

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.