title: HMGB1 was a pivotal synergistic effecor for CpG oligonucleotide to enhance the progression of human lung cancer cells.
abstract: High-mobility group box 1 (HMGB1) has been implicated in a variety of biologically important processes, including transcription, DNA repair, differentiation, development, and extracellular signaling. However, the potential role of HMGB1 in tumor biology still remains intractable. Our previous study showed that TLR9 response to CpG oligonucleotide (ODN) in 95D human lung cancer cells could enhance their growth and invasive potential in vitro and in vivo. Here we found that CpG ODN stimulation to 95D cells induced the secretion of HMGB1 in a dose dependent manner. We further showed that blockade of extracellular HMGB1 using A box peptide and ethyl pyruvate significantly abrogated the CpG ODN enhanced progression of 95D cells. Interestingly, we found that HMGB1 alone or acted synergistic with CpG ODN could enhance the progression of 95D cells. Notably, we revealed that RAGE and TLR4 were critical for HMGB1 to exert the synergistic function. We observed a MyD88-dependent upregulation of matrix metalloproteinase (MMP) 2, MMP9 and cyclin-dependent kinase (CDK) 2 in 95D cells in response to HMGB1. These findings might further our understanding of TLR9 signaling in tumor biology and be helpful for developing HMGB1-based strategy against lung cancer.
authors.affiliation: Department of Chest Medicine, Qingdao Chest Hospital, Shandong, China.
authors.forename: Chunhong
authors.initials: C
authors.lastname: Wang
authors.forename: Guangru
authors.initials: G
authors.lastname: Fei
authors.forename: Zhongmin
authors.initials: Z
authors.lastname: Liu
authors.forename: Qinchuan
authors.initials: Q
authors.lastname: Li
authors.forename: Zengguang
authors.initials: Z
authors.lastname: Xu
authors.forename: Tao
authors.initials: T
authors.lastname: Ren
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor / Q000187:drug effects; D002465:Cell Movement; D049109:Cell Proliferation; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism; D055785:Gene Knockdown Techniques; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D058990:Molecular Targeted Therapy; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D011773:Pyruvates / Q000494:pharmacology; D034622:RNA Interference; D000067759:Receptor for Advanced Glycation End Products / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000378:metabolism / Q000819:agonists; D015854:Up-Regulation
chemical_list: D000970:Antineoplastic Agents; C526902:CpG ODN 2216; D024243:HMGB1 Protein; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D009838:Oligodeoxyribonucleotides; D011773:Pyruvates; D000067759:Receptor for Advanced Glycation End Products; C495342:TLR2 protein, human; C495345:TLR4 protein, human; C495371:TLR9 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9; C046522:ethyl pyruvate; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9