Background: Histidine-rich glycoprotein (HRG), a multifunctional plasma protein, has a regulatory role in homeostasis, angiogenesis, and immunity;which in turn could greatly affect tumor control and metastasis. Object...Background: Histidine-rich glycoprotein (HRG), a multifunctional plasma protein, has a regulatory role in homeostasis, angiogenesis, and immunity;which in turn could greatly affect tumor control and metastasis. Objectives: To assess the possible role of HRG in acute lymphoblastic leukemia (ALL) tumorgenesis and follow-up. Design and Methods: HRG was quantitatively measured in serum by ELISA and its expression was assessed by real-time PCR (qPCR) in 35 patients with ALL and compared to same 25 ALL patients after induction therapy and 30 age and sex matched healthy control subjects. Results: HRG-serum protein (at cutoff value 63.55 pg/ml) and HRG-RNA (at cut-off value 0.955) were positive in all ALL patients before therapy, but in only 76% after therapy for HRG-protein and 60% for HRG-RNA and they could not be detected in the control group;P < 0.001. Additionally, the serum HRG level showed a significant positive correlation with its expression level, bone marrow blast percentage, peripheral blood blast count, P < 0.01. Also its serum and expression levels were positively related to the poor risk Philadelphia chromosome;P < 0.01. Conclusions: HRG (protein and RNA) might be considered as a novel diagnostic and prognostic marker in ALL. HRG-serum protein level, detected by simple methodology of ELISA, has more significant advantages than its expression level, motivating its application in large clinical studies as a potential marker.展开更多
Histidine-rich glycoprotein(HRGP)is a relatively less known glycoprotein,but it is abundant in plasma with a multidomain structure,which allows it to interact with many ligands and regulate various biological processe...Histidine-rich glycoprotein(HRGP)is a relatively less known glycoprotein,but it is abundant in plasma with a multidomain structure,which allows it to interact with many ligands and regulate various biological processes.HRGP ligands includes heme,Zn^(2+),thrombospondin,plasmin/plasminogen,heparin/heparan sulfate,fibrinogen,tropomyosin,IgG,FcγR,C1q.In many conditions,the histidine-rich region of HRGP strengthens ligand binding following interaction with Zn^(2+)or exposure to low pH,such as sites of tissue injury or tumor growth.The multidomain structure and diverse ligand binding attributes of HRGP indicates that it can act as an extracellular adaptor protein,connecting with different ligands,especially on cell surfaces.Also,HRGP can selectively target IgG,which blocks the production of soluble immune complexes.The most common cell surface ligand of HRGP is heparan sulfate proteoglycan,and the interaction is also potentiated by elevated Zn^(2+)concentration and low pH.Recent reports have shown that HRGP can modulate macrophage polarization and possibly regulate other physiological processes such as angiogenesis,anti-tumor immune response,fibrinolysis and coagulation,soluble immune complex clearance and phagocytosis of apoptotic/necrosis cells.In addition,it has also been reported that HRGP has antibacterial and anti-HIV infection effects and may be used as a novel clinical biomarker accordingly.This review outlines the molecular,structural and biological properties of HRGP as well as presenting an update on the function of HRGP in various physiological processes.展开更多
文摘Background: Histidine-rich glycoprotein (HRG), a multifunctional plasma protein, has a regulatory role in homeostasis, angiogenesis, and immunity;which in turn could greatly affect tumor control and metastasis. Objectives: To assess the possible role of HRG in acute lymphoblastic leukemia (ALL) tumorgenesis and follow-up. Design and Methods: HRG was quantitatively measured in serum by ELISA and its expression was assessed by real-time PCR (qPCR) in 35 patients with ALL and compared to same 25 ALL patients after induction therapy and 30 age and sex matched healthy control subjects. Results: HRG-serum protein (at cutoff value 63.55 pg/ml) and HRG-RNA (at cut-off value 0.955) were positive in all ALL patients before therapy, but in only 76% after therapy for HRG-protein and 60% for HRG-RNA and they could not be detected in the control group;P < 0.001. Additionally, the serum HRG level showed a significant positive correlation with its expression level, bone marrow blast percentage, peripheral blood blast count, P < 0.01. Also its serum and expression levels were positively related to the poor risk Philadelphia chromosome;P < 0.01. Conclusions: HRG (protein and RNA) might be considered as a novel diagnostic and prognostic marker in ALL. HRG-serum protein level, detected by simple methodology of ELISA, has more significant advantages than its expression level, motivating its application in large clinical studies as a potential marker.
基金This project is supported by the(No.20204Y0012)Project of Shanghai Municipal Health CommissionNational Key R&D Program of China(No.2017YFC0908100)+1 种基金W410170015,Cohort Study of HCC and Liver Diseases,Double First-Class Fundation,Shanghai Jiao Tong University2017ZZ01018,Overall Leverage Clinical Medicine Center,NHFPC Fundation.
文摘Histidine-rich glycoprotein(HRGP)is a relatively less known glycoprotein,but it is abundant in plasma with a multidomain structure,which allows it to interact with many ligands and regulate various biological processes.HRGP ligands includes heme,Zn^(2+),thrombospondin,plasmin/plasminogen,heparin/heparan sulfate,fibrinogen,tropomyosin,IgG,FcγR,C1q.In many conditions,the histidine-rich region of HRGP strengthens ligand binding following interaction with Zn^(2+)or exposure to low pH,such as sites of tissue injury or tumor growth.The multidomain structure and diverse ligand binding attributes of HRGP indicates that it can act as an extracellular adaptor protein,connecting with different ligands,especially on cell surfaces.Also,HRGP can selectively target IgG,which blocks the production of soluble immune complexes.The most common cell surface ligand of HRGP is heparan sulfate proteoglycan,and the interaction is also potentiated by elevated Zn^(2+)concentration and low pH.Recent reports have shown that HRGP can modulate macrophage polarization and possibly regulate other physiological processes such as angiogenesis,anti-tumor immune response,fibrinolysis and coagulation,soluble immune complex clearance and phagocytosis of apoptotic/necrosis cells.In addition,it has also been reported that HRGP has antibacterial and anti-HIV infection effects and may be used as a novel clinical biomarker accordingly.This review outlines the molecular,structural and biological properties of HRGP as well as presenting an update on the function of HRGP in various physiological processes.
