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Lysyl oxidase (LOX) family is a group of copper-containing amine oxidases composed of LOX and LOX-like proteins (LOXL1, LOXL2, LOXL3, and LOXL4). It is overexpressed in tumor tissue and promotes tumor metastasis through covalent cross-linking of extracellular matrix, with the functions of cell growth control, tumor inhibition, senescence, and chemotaxis. In recent years, more and more evidence has shown that LOX family members play a key role in the pathogenesis of hepatocellular carcinoma (HCC), suggesting that they have great potential as therapeutic targets. This article reviews the role of LOX family members in the development and progression of HCC and the intervention effect of traditional Chinese medicine extracts on HCC by regulating LOX family, in order to provide a reference for further research on the prevention and treatment of HCC.
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BACKGROUND: Intratumoral fibrosis (ITF) is a frequent histologic finding in solid organ tumors. Renal cell carcinoma (RCC) is a highly vascularized tumor with different shapes and degrees of ITF and inflammation. ITF is a poor prognostic factor, especially in breast cancer, and is related to intratumoral necrosis (ITN) and intratumoral inflammation (ITI). However, the significance of ITF in RCC has not been fully studied. In this study, we evaluate the relationships between ITF and other clinicopathologic parameters associated with RCC prognosis. METHODS: ITF was evaluated in 204 clear cell renal cell carcinoma (CCRCC) specimens according to presence and grade of fibrosis, degree of ITI, and presence of ITN. Lysyl oxidase (LOX) expression in tumor cells was also evaluated with clinicopathologic parameters. RESULTS: Among 204 CCRCC cases, 167 (81.7%) showed ITF, 71 (34.8%) showed ITI, 35 (17.2%) showed ITN, and 111 (54.4%) showed LOX expression. ITF correlated with Fuhrman nuclear grade (p = .046), lymphovascular invasion (LVI) (p = .027), and ITN (p = .036). Patients with ITF had a poor five-year overall survival rate (p = .104). CONCLUSIONS: ITF is related to other poor prognostic factors in CCRCC, such as Fuhrman nuclear grade, ITN, and LVI, but ITF itself had no significant correlation with prognosis of CCRCC.
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Humans , Breast Neoplasms , Carcinoma, Renal Cell , Fibrosis , Inflammation , Necrosis , Prognosis , Protein-Lysine 6-Oxidase , Survival RateABSTRACT
Background Researches showed that transforming growth factor-β2 (TGF-β2) promotes the activity of human Tenon capsular fibroblasts (TFs),which plays a role in the scarring of filtering blebs after antiglaucoma surgery.However,its mechanism is not fully clear.Lysyl oxidases (LOXs) are important extracellular matrix proteases which can catalyze the cross-linking of collagen and elastin.Investigating the impact of TGF-β2 on the expression of LOXs has a great significance for the understanding of the pathogenesis of filtering bleb scarring and its prevention.Objective This study was to investigate the effect of TGF-β2 on the expression of LOXs in cultured human TFs.Methods The TFs at 4-8 generations were divided into normal control group and different concentrations of TGF-β2 treated-groups,and 100,200,400,800 μ1 of TGF-β2 with the final concentration of 2,4,8 and 16 ng/ml was added into the medium to treat human TFs respectively for 24 hours.The LOXs in the cells were detected by Western blot to determine the optimal dose of TGF-β2.The 4 ng/ml TGF-β2(200 μ1) was used to treat human TFs for 6,12,24 and 48 hours respectively,and the change of LOXs expression in the cells over time was assayed by Western blot.The expression and distribution of LOX protein in the normal cells and TGF-β2-treated cells was detected by using immunofluorescence technique.This study was approved by Daping Hospital of Third Military Medical University Ethic Commission.The guardians of the patients who offered the specimen knew the purpose of the study and signed informed consent.Results Western blot assay showed that the expressions of LOX,LOXL1,LOXL2,LOXL3 and LOXL4 in the cells were gradually elevated from the normal control group and 2,4,8,16 ng/ml TGF-β2-treated groups,showing significant differences among the groups (F =37.338,13.438,31.067,11.767,15.167,all at P＜0.01).The expression of LOXL2 protein in the cells was 0.68±0.07,1.09±0.10,1.32±0.07,1.50± 0.06 and 1.89±0.12 in the normal control group and 6-,12-,24-and 48-hour groups respectively after 4 ng/ml TGF-β2 treatment,with a significant increase over time (F =82.832,P=0.000).The expression of LOX was weak in the normal cultured TFs,while the fluorescence intensity of LOX expression was evidently enhanced in the cytoplasm of the cells in the TGF-β2-treated group.Conclusions TGF-β2 upregulates the expressions of LOXs in human TFs in a dose-and time-dependent manner,which probably offers a basis for the further study on the prevention of filtering bleb scarring after glaucoma surgery.
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Objective To investigate the effect of lysyl oxidase (LOX) gene expression on proliferation, invasion and radiotherapy sensitivity in laryngeal cancer Hep-2 cells. Methods Hep-2 cells were divided into control group (normal cultured), negative control group (transfection reagent) and transfection group (LOX siRNA transfected). The expressions of LOX, Ki-67, PCNA, MMP-2 and MMP-9 mRNA were detected by real time-PCR and Western blot methods. The cell sur-vival rate and apoptosis irradiated by different doses of X-rays (0, 3, 6, 9, 12, 15 and 18 Gy) were detected by MTT and flow cytometry (FCM). Results The expression levels of LOX, Ki-67, PCNA, MMP-2 and MMP-9 protein and mRNA were sig-nificantly lower in Hep-2 cells after transfection than those of control group and negative control group (P<0.05). The cell survival rate was significantly inhibited 24 hours after irradiation (12, 15 and 18 Gy) in a dose-dependent manner (P<0.05). The apoptotic rate of transfection cells combined with radiotherapy was significantly higher than that of control and the nega-tive control groups (%:79.11 ± 1.26 vs 5.01 ± 1.02, 4.95 ± 1.12, 43.21 ± 2.1,P<0.05). Conclusion The expression of LOX can be down-regulated after LOX siRNA transfection, inhibiting proliferation and enhancing radiosensitivity, which may be related to the down-regulation of Ki-67, PCNA, MMP-2 and MMP-9 protein expression.
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Lysyal oxidase (LOX),a cooper dependent monoamine oxidase,can stabilize the extracellular matrix and is closely related to the tumor cell differentiation,vicious transformation and invasiveness.LOX is secreted into extracellular,and it is resolved into a small fragment by sol protease,which is lysyal oxidase propeptide (LOX-PP).According to research,LOX-PP has its own structure and physiological functions,which can inhibit the growth of tumor cells.LOX-PP also plays a significant role in the generation and progression of tumor,which is likely to be a new therapeutic target.
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Lysyl oxidase-like protein 2 (LOXL2) is one of the lysyl oxidases (LOX) families.At present,most of scholars consider that LOXL2 is a neoplasm metastasis gene,whereas some others belleve that LOXL2 is a neoplasm suppressor gene.Studies found that LOXL2 gene combined with other oncogenes promotes neoplasm invasion,metastasis and indicates a poor prognosis.Related researches provide new ideas for judging tumor metastasis and prognosis and looking for new targets for cancer therapy.
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Objective To investigate expression of elastin,lysyl oxidase (LOX)and elafin in cardinal ligament of women with pelvic organ prolapse(POP) so as to determine their contributions to POP.Methods The cardinal ligament samples were obtained from 60 POP subjects and 60 non-POP control women undergoing hysterectomy.RT-PCR was used to verify the mRNA level of elastin,LOX and elafin.The protein concentration of the three genes was determined by western blotting technique,electrophoretic separation and quantification.Results The premenopansal and postmenopausal POP groups demonstrated significantly decreased expressions of elastin in cardinal ligament both in mRNA and protein levels than control group (mRNA 0.42±0.22,0.26±0.20 versus 0.79±0.30,0.63±0.23 ; protein 0.44±0.32,0.20±0.19 versus 0.89±0.27,0.78±0.25; P＜0.05).There was an identical tendency in the expression of LOX (mRNA 0.37±0.18,0.20±0.14 versus 0.65±0.22,0.53±0.20; protein 0.45±0.27,0.26±0.21 versus 0.85±0.39,0.69±0.31 ; P＜0.05).In POP group,the mRNA and protein levels of elastin and LOX in postmenopansal patients were significantly lower than premenopansal patients (P＜0.05).Inversely,POP group demonstrated an increased expression of elafin in cardinal ligament both in mRNA and protein levels than corresponding control group (mRNA 1.33±0.35,1.47±0.37 versus 0.62±0.25,0.55±0.24; protein 0.85±0.30,0.76±0.35 versus 0.21±0.15,0.29±0.22; P＜0.05). There was no significant difference in the expression of elafin between premenopansal and postmenopausal POP groups either in mRNA or protein levels(P＞0.05).There was a positive correlation between elastin and LOX both in mRNA and protein levels in POP group(r=0.9959,0.9708; P＜0.05),but there was no correlation between elastin and elafin(r=-0.0402,-0.0365;P＞0.05).Conclusions The results suggest that the decreased expression of elastin and LOX and the increased expression of elafin in the cardinal ligaments may contribute to POP.
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Objective To determine the relationships between maternal serum copper,amniotic copper,lysyl oxidase (LOX) and collagen Ⅲ in pregnant women with premature rupture of membranes (PROM) and without PROM.Methods One hundred women with PROM were enrolled in this study,and divided into 37-42 weeks,34-36~ +6 weeks and 28-33~ +6 weeks according to gestational age. One hundred non-PROM pregnancies matching the same gestational ages were recruited as control group. Copper of maternal serum and amnion in two groups were compared by FAAS method. Amniotic LOX was analyzed by fluorometry. Amniotic collagen Ⅲ was detected by immunohistochemical method and computer image analysis system(absorbance,A). Linear correlation analysis was used to explore the relationships between maternal serum copper,amniotic copper,LOX and collagen Ⅲ. Results (1)For 37-42 weeks pregnant women,serum copper was correlated positively with amniotic copper in two groups, r= 0.82(P0.05),but amniotic LOX and collagen Ⅲ decreased significantly compared with controls, being [(0.53?0.10)?g/g vs (0.75?0.10)?g/g,P