急性髓系白血病HGFA、Matriptase、HAI-1、HAI-2表达水平及临床意义
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摘要
目的:探讨HGFA、Matriptase、HAI-1、HAI-2在急性髓系白血病患者中的表达水平及其临床意义。方法:收集91例急性髓系白血病初治患者、41例急性髓系白血病缓解患者和32例正常人的骨髓标本,利用实时荧光定量RT-PCR(qRT-PCR)法检测髓系白血病细胞HGFA、Matriptase、HAI-1、HAI-2 mRNA表达水平;比较上述基因在人急性髓系白血病患者初治组和缓解组以及健康对照组中的表达情况;分析其表达情况与其临床特征的相关性。结果:在AML初治组HGFA水平高于健康对照组(P=0.010);而HAI-2 mRNA水平则低于健康对照组(P=0.0158),但均与AML缓解组无统计学差异。HAI-1、Matriptase mRNA水平在各组中均无明显差异。在高白细胞组中HAI-2 mRNA表达较低(P=0.03902)。结论:HGF/c-Met信号系统在AML中的异常激活,有可能是其上游的调控因子HGFA表达增高和HAI-2表达降低的结果。
Objective: To investigate the expression and clinical significances of HGFA,Matriptase,HAI-1 and HAI-2 in patients with acute myeloid leukemia( AML). Methods: The bone marrow samples from 91 AML patients,41 AML patients in complete remission,and 32 normal controls were collected. Real-time fluorescence quantitative RTPCR( qRT-PCR) was used to detect the mRNA expressions levels of HGFA,Matriptase,HAI-1,HAI-2. The expressions of these genes were compared among AML untreated group,the complete remission group and the healthy control group. The correlation of their expression with clinical characteristics was analyzed. Results: The level of HGFA in the AML untreated group was higher than that in the healthy control group( P < 0. 05),while the HAI-2 mRNA level was lower than that in the healthy control group( P < 0. 05). The mRNA levels of HAI-1 and Matriptase were not changed significantly in all groups. The HAI-2 mRNA expression level was significantly lower in the high white blood cell group( P < 0. 05). Conclusion: The abnormal activation of HGF/c-Met signaling system in AML may result from the increase of HGFA expression and the decrease of HAI-2 expression of the upstream regulatory factors.
Objective: To investigate the expression and clinical significances of HGFA,Matriptase,HAI-1 and HAI-2 in patients with acute myeloid leukemia( AML). Methods: The bone marrow samples from 91 AML patients,41 AML patients in complete remission,and 32 normal controls were collected. Real-time fluorescence quantitative RTPCR( qRT-PCR) was used to detect the mRNA expressions levels of HGFA,Matriptase,HAI-1,HAI-2. The expressions of these genes were compared among AML untreated group,the complete remission group and the healthy control group. The correlation of their expression with clinical characteristics was analyzed. Results: The level of HGFA in the AML untreated group was higher than that in the healthy control group( P < 0. 05),while the HAI-2 mRNA level was lower than that in the healthy control group( P < 0. 05). The mRNA levels of HAI-1 and Matriptase were not changed significantly in all groups. The HAI-2 mRNA expression level was significantly lower in the high white blood cell group( P < 0. 05). Conclusion: The abnormal activation of HGF/c-Met signaling system in AML may result from the increase of HGFA expression and the decrease of HAI-2 expression of the upstream regulatory factors.
引文
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11陈建华,陈元仲,吴勇.经裸鼠体内多次传代所致的高致瘤HL-60细胞模型的建立及其细胞生物学特征.中国实验血液学杂志,2010;18(2):350-354.
12 Kataoka H,Hamasuna R,Itoh H,et al.Activation of hepatocyte growth factor/scatter factor in colorectal carcinoma.Cancer Res,2000;60(21):6148-6159.
13 Tjin EP,Derksen PW,Kataoka H,et al.Multiple myeloma cells catalyze hepatocyte growth factor(HGF)activation by secreting the serine protease HGF-activator.Blood,2004;104(7):2172-2175.
14 Tjin EP,Groen RW,Vogelzang I,et al.Functional analysis of HGF/MET signaling and aberrant HGF-activator expression in diffuse large B-cell lymphoma.Blood,2006;107(2):760-768.
15 Wu SR,Teng CH,Tu YT,et al.The Kunitz Domain I of hepatocyte growth factor activator inhibitor-2 inhibits matriptase activity and invasive ability of human prostate cancer cells.Sci Rep,2017;7(1):15101.
16 Kataoka H,Shimomura T,Kawaguchi T,et al.Hepatocyte growth factor activator inhibitor type 1 is a specific cell surface binding protein of hepatocyte growth factor activator(HGFA)and regulates HGFAactivity in the pericellular microenvironment.J Biol Chem,2000;275(51):40453-40462.
17 Ning T,Zhang H,Wang X,et al.miR-221 and miR-222 synergistically regulate hepatocyte growth factor activator inhibitor type 1 to promote cell proliferation and migration in gastric cancer.Tumour Biol,2017;39(6):1010428317701636.
18 Roversi FM,Olalla Saad ST,Machado-Neto JA.Serine peptidase inhibitor Kunitz type 2(SPINT2)in cancer development and progression.Biomed Pharmacother,2018,101:278-286.
19 Sakaguchi H,Seki S,Tsubouchi H,et al.Ultrastructural location of human hepatocyte growth factor in human liver.Hepatology,1994;19(5):1157-1163.
2 De Silva DM,Roy A,Kato T,et al.Targeting the hepatocyte growth factor/Met pathway in cancer.Biochem Soc Trans,2017;45(4):855-870.
3 Scagliotti GV,Novello S,von Pawel J.The emerging role of MET/HGF inhibitors in oncology.Cancer Treat Rev,2013;39(7):793-801.
4 Trusolino L,Bertotti A,Comoglio PM.MET signaling:principles and functions in development,organ regeneration and cancer.Nat Rev Mol Cell Biol,2010;11(12):834-848.
5 Gohda E,Nakamura S,Yamamoto I,et al.Hepatocyte growth factor---pleiotropic cytokine produced by human leukemia cells.Leuk Lymphoma,1995;19(3-4):197-205.
6 Kentsis A,Reed C,Rice KL,et al.Autocrine activation of the METreceptor tyrosine kinase in acute myeloid leukemia.Nat Med,2012;18(7):1118-1122.
7 Guo JR,Li W,Wu Y,et al.Hepatocyte growth factor promotes proliferation,invasion,and metastasis of myeloid leukemia cells through PI3K-AKT and MAPK/ERK signaling pathway.Am J Transl Res,2016;8(9):3630-3644.
8 Kawaguchi M,Kataoka H.Mechanisms of hepatocyte growth factor activation in cancer tissues.Cancers(Basel),2014;6(4):1890-1904.
9 Kataoka H,Kawaguchi M.Hepatocyte growth factor activator(HGFA):pathophysiological functions in vivo.FEBS J,2010;277(10):2230-2237.
10 Wader KF,Fagerli UM,Holt RU,et al.Elevated serum concentrations of activated hepatocyte growth factor activator in patients with multiple myeloma.Eur J Haematol,2008;81(5):380-383.
11陈建华,陈元仲,吴勇.经裸鼠体内多次传代所致的高致瘤HL-60细胞模型的建立及其细胞生物学特征.中国实验血液学杂志,2010;18(2):350-354.
12 Kataoka H,Hamasuna R,Itoh H,et al.Activation of hepatocyte growth factor/scatter factor in colorectal carcinoma.Cancer Res,2000;60(21):6148-6159.
13 Tjin EP,Derksen PW,Kataoka H,et al.Multiple myeloma cells catalyze hepatocyte growth factor(HGF)activation by secreting the serine protease HGF-activator.Blood,2004;104(7):2172-2175.
14 Tjin EP,Groen RW,Vogelzang I,et al.Functional analysis of HGF/MET signaling and aberrant HGF-activator expression in diffuse large B-cell lymphoma.Blood,2006;107(2):760-768.
15 Wu SR,Teng CH,Tu YT,et al.The Kunitz Domain I of hepatocyte growth factor activator inhibitor-2 inhibits matriptase activity and invasive ability of human prostate cancer cells.Sci Rep,2017;7(1):15101.
16 Kataoka H,Shimomura T,Kawaguchi T,et al.Hepatocyte growth factor activator inhibitor type 1 is a specific cell surface binding protein of hepatocyte growth factor activator(HGFA)and regulates HGFAactivity in the pericellular microenvironment.J Biol Chem,2000;275(51):40453-40462.
17 Ning T,Zhang H,Wang X,et al.miR-221 and miR-222 synergistically regulate hepatocyte growth factor activator inhibitor type 1 to promote cell proliferation and migration in gastric cancer.Tumour Biol,2017;39(6):1010428317701636.
18 Roversi FM,Olalla Saad ST,Machado-Neto JA.Serine peptidase inhibitor Kunitz type 2(SPINT2)in cancer development and progression.Biomed Pharmacother,2018,101:278-286.
19 Sakaguchi H,Seki S,Tsubouchi H,et al.Ultrastructural location of human hepatocyte growth factor in human liver.Hepatology,1994;19(5):1157-1163.