PMID- 28395594 OWN - NLM STAT- MEDLINE DCOM- 20171009 LR - 20171009 IS - 1607-8454 (Electronic) IS - 1024-5332 (Linking) VI - 22 IP - 9 DP - 2017 Oct TI - Upregulation of ADAM12 contributes to accelerated cell proliferation and cell adhesion-mediated drug resistance (CAM-DR) in Non-Hodgkin's Lymphoma. PG - 527-535 LID - 10.1080/10245332.2017.1312205 [doi] AB - OBJECTIVE: ADAM12 is a member of a disintegrin and metalloproteinase family and has been reported to participate in the development of variety of tumors. However, the role of ADAM12 in Non-Hodgkin Lymphoma (NHL) has not been investigated. The present study was undertaken to determine the expression and biologic function of ADAM12 in human NHL. METHODS: First, we constructed a model of cell adhesion in NHL, the mRNA, and protein level of ADAM12 in suspension and the adhesion model was analyzed by RT-PCR and western blot. Then, flow cytometry assay and western blot were used to investigate the mechanism of ADAM12 in the proliferation of NHL cells. In vitro, after using siRNA interfering ADAM12 expression, we performed adhesion assay and cell viability assay to determine the effect of ADAM12 on adhesive rate and drug sensitivity. RESULTS: ADAM12 was lowly expressed in suspended cells and highly expressed in adherent NHL cells. In addition, ADAM12 was positively correlated with the proliferation and apoptosis of NHL cells by regulating the expression of p-AKT and p-GSK-3beta. Furthermore, ADAM12 promoted cell adhesion-mediated drug resistance (CAM-DR) in DLBCL via AKT signaling pathway. CONCLUSION AND DISCUSSION: Our data support a role for ADAM12 in NHL cell proliferation, adhesion, and drug resistance, and it may pave the way for a novel therapeutic approach for CAM-DR in NHL. FAU - Yin, Haibing AU - Yin H AD - a Department of Pathology , Affiliated Cancer Hospital of Nantong University , Nantong , PR China. FAU - Zhong, Fei AU - Zhong F AD - b Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University , Nantong , PR China. FAU - Ouyang, Yu AU - Ouyang Y AD - b Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University , Nantong , PR China. FAU - Wang, Qiru AU - Wang Q AD - b Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University , Nantong , PR China. FAU - Ding, Linlin AU - Ding L AD - b Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University , Nantong , PR China. FAU - He, Song AU - He S AD - a Department of Pathology , Affiliated Cancer Hospital of Nantong University , Nantong , PR China. LA - eng PT - Journal Article DEP - 20170410 PL - England TA - Hematology JT - Hematology (Amsterdam, Netherlands) JID - 9708388 RN - 0 (Antineoplastic Agents) RN - 0 (Biomarkers, Tumor) RN - 0 (RNA, Small Interfering) RN - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 3.4.24.- (ADAM12 Protein) SB - IM MH - ADAM12 Protein/*genetics MH - Animals MH - Antineoplastic Agents/pharmacology/therapeutic use MH - Apoptosis/drug effects/genetics MH - Biomarkers, Tumor MH - Cell Adhesion/*genetics MH - Cell Cycle/drug effects/genetics MH - Cell Line, Tumor MH - Cell Proliferation MH - Drug Resistance, Neoplasm/*genetics MH - *Gene Expression Regulation, Neoplastic MH - Glycogen Synthase Kinase 3 beta/genetics/metabolism MH - Humans MH - Lymphoma, Non-Hodgkin/drug therapy/*genetics/metabolism MH - Mice MH - Proto-Oncogene Proteins c-akt/genetics/metabolism MH - RNA Interference MH - RNA, Small Interfering/genetics MH - Signal Transduction OTO - NOTNLM OT - ADAM12 OT - AKT/PI3K signaling pathway OT - CAM-DR OT - cell proliferation NHL EDAT- 2017/04/12 06:00 MHDA- 2017/10/11 06:00 CRDT- 2017/04/12 06:00 PHST- 2017/04/12 06:00 [pubmed] PHST- 2017/10/11 06:00 [medline] PHST- 2017/04/12 06:00 [entrez] AID - 10.1080/10245332.2017.1312205 [doi] PST - ppublish SO - Hematology. 2017 Oct;22(9):527-535. doi: 10.1080/10245332.2017.1312205. Epub 2017 Apr 10.