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Lung T. Yam - One of the best experts on this subject based on the ideXlab platform.
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applications and performance of monoclonal antibodies to human tartrate resistant Acid Phosphatase
Journal of Immunological Methods, 2011Co-Authors: Silvia Potenziani D Pradella, Tsu Yi Chao, Lung T. Yam, Stephen P. Slone, Ranga N Parthasarathy, Anthony J. JanckilaAbstract:Abstract Background Tartrate-Resistant Acid Phosphatase (TRACP) is an enzyme common to cells of the mononuclear phagocyte system and a clinically relevant biomarker for osteoclasts and inflammatory macrophages. The purpose was to assess applications and performance of six anti-TRACP monoclonal antibodies. Methods Mab9 C5, 14 G6, 162, 203, 220, and 89 were used as capture and detection antibodies in quantitative immunoassay, and for western blot (WB), immunoprecipitation, and immunohistochemistry of paraffin sections containing chronic inflammatory infiltrates. The clinical performance of mab14 G6 for immunoassay of serum TRACP5b activity was compared to two commercial kit methods. Results Mab9 C5 is useful for WB and immunohistochemistry methods only. Mab14G6, 162, and 203 are useful for quantitative immunoassay and immunoprecipitation, however, mab203 causes inactivation of enzymatic activity. Mab220 and 89 are specific for TRACP5a and useful in all applications. Mab14G6 has similar clinical sensitivity and specificity as two commercial methods. Conclusions TRACP is an important marker in osteoimmunology. Specific antibodies with unique specificity for TRACP isoforms and defined applications will be valuable for clinical evaluation of bone metabolic, inflammatory and autoimmune diseases and will aid in basic research of TRACP biochemistry and biology.
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Applications and performance of monoclonal antibodies to human tartrate resistant Acid Phosphatase.
Journal of immunological methods, 2011Co-Authors: Silvia Potenziani D Pradella, Tsu Yi Chao, Lung T. Yam, Stephen P. Slone, Ranga N Parthasarathy, Anthony J. JanckilaAbstract:Tartrate-Resistant Acid Phosphatase (TRACP) is an enzyme common to cells of the mononuclear phagocyte system and a clinically relevant biomarker for osteoclasts and inflammatory macrophages. The purpose was to assess applications and performance of six anti-TRACP monoclonal antibodies. Mab9C5, 14G6, 162, 203, 220, and 89 were used as capture and detection antibodies in quantitative immunoassay, and for western blot (WB), immunoprecipitation, and immunohistochemistry of paraffin sections containing chronic inflammatory infiltrates. The clinical performance of mab14G6 for immunoassay of serum TRACP5b activity was compared to two commercial kit methods. Mab9C5 is useful for WB and immunohistochemistry methods only. Mab14G6, 162, and 203 are useful for quantitative immunoassay and immunoprecipitation, however, mab203 causes inactivation of enzymatic activity. Mab220 and 89 are specific for TRACP5a and useful in all applications. Mab14G6 has similar clinical sensitivity and specificity as two commercial methods. TRACP is an important marker in osteoimmunology. Specific antibodies with unique specificity for TRACP isoforms and defined applications will be valuable for clinical evaluation of bone metabolic, inflammatory and autoimmune diseases and will aid in basic research of TRACP biochemistry and biology. Published by Elsevier B.V.
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Tartrate-Resistant Acid Phosphatase as an Immunohistochemical Marker for Inflammatory Macrophages
American journal of clinical pathology, 2007Co-Authors: Anthony J. Janckila, Sheron C. Lear, Alvin W. Martin, Stephen P. Slone, Lung T. YamAbstract:Human serum contains 2 isoforms of type-5 Tartrate-Resistant Acid Phosphatase (TRACP): 5a and 5b. TRACP-5b is osteoclastic. Our goal was to determine if serum TRACP-5a could originate from inflammatory macrophages (MPhi). We stained 246 paraffin-embedded tissue samples for TRACP using monoclonal antibody 9C5 (mab9C5) to isoforms 5a and 5b and a novel mab220 specific to isoform 5a. CD68 and lysozyme were also stained. MPhi of chronic and granulomatous inflammation and in tissues that undergo strong antigenic stimulation were strongly positive for TRACP, more so with mab220 than with mab9C5. Noninflammatory MPhi in lymph node sinuses or germinal centers and red pulp MPhi of spleen were weak or negative for TRACP. Marginal zone lymphocytes and sebaceous glands of skin were weakly positive for TRACP. Tissue mast cells displayed strong TRACP staining. Neuroendocrine cells of gastrointestinal tissues were strongly immunoreactive with mab9C5 but negative with mab220. Restricted expression of TRACP primarily in inflammatory MPhi supports our hypothesis that circulating TRACP-5a could be a biomarker of chronic inflammatory disease activity.
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Development of immunoassays for serum Tartrate-Resistant Acid Phosphatase isoform 5a.
Clinica Chimica Acta, 2005Co-Authors: Tsu Yi Chao, Su Huei Lee, Lung T. Yam, David H. Neustadt, Mary M. Chen, Uzma A. Chaudhry, Anthony J. JanckilaAbstract:Abstract Background Serum Tartrate-Resistant Acid Phosphatase (TRACP) consists of 2 structurally related isoforms, TRACP 5a and 5b. TRACP 5b is from bone-resorbing osteoclasts. TRACP 5a may be a macrophage product of inflammation. We used a novel antibody to TRACP 5a to standardize immunoassays for serum TRACP 5a activity and protein. Methods Biotinylated anti-TRACP antibodies were used to immobilize serum TRACP isoforms. TRACP activity was measured using 4-nitrophenyl phosphate as substrate. TRACP 5a protein was measured with an independent peroxidase-conjugated anti-TRACP antibody. Immunoassays were standardized for linearity of serum dose response, sensitivity and precision. Reference ranges for TRACP 5a were established from serum of 50 healthy males and 50 healthy age-matched females. Serum TRACP 5a activity and protein were determined in 29 cases of rheumatoid arthritis. Results Serum matrix interference in both TRACP 5a assays required dilution to 10% serum to approach linearity. Intra-assay and inter-assay CV% were Conclusions Although TRACP 5a and 5b are related biosynthetically, their circulating levels in healthy humans were independent, suggesting differential regulation of expression. In chronic diseases, increased TRACP 5a may represent pathological processes of inflammation unrelated to bone metabolism.
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Flow cytoenzymology of intracellular Tartrate-Resistant Acid Phosphatase
The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society, 2003Co-Authors: Anthony J. Janckila, Wen Kuang Yang, Ruey-jen Lin, Chia Jen Tseng, Hsin-yu Chang, Jia Ming Chang, Lung T. YamAbstract:SUMMARY Tartrate-Resistant Acid Phosphatase (TRACP) is a cytochemical marker for hairy cell leukemia, macrophages, dendritic cells, and osteoclasts. Our purpose was to develop multicolor cytofluorometric methods to evaluate intracellular TRACP enzymic activity using a fluorogenic cytochemical reaction in combination with immunochemical stains for distinct surface membrane antigens. Monocyte-derived dendritic cells (DCs) were the model TRACP-expressing cells studied. Intracellular TRACP activity was disclosed using naphthol-ASBI phosphate as substrate with fast red-violet LB salt as coupler for the reaction product. Before the TRACP enzymic reaction, surface antigens, CD86 and CD11c of DCs, were bound with specific fluorescent antibodies to test compatibility of surface labeling and intracellular staining. TRACP activity varied in DCs from donor to donor but was reproducible on repeated examinations of each sample. Samples could be stained for simultaneous analysis of surface antigens and intracellular TRACP activity, provided certain technical details were observed. The TRACP reaction time should not exceed 9 min and the cell number should not exceed 2 � 10 5 /100 � l test. Fluorescent surface labels did not affect the intensity of the TRACP stain, but the intensity of some surface labels may be diminished by elution of low-affinity antibodies during the TRACP reaction. Readjustment of the threshold settings in triple-labeled cells is needed to compensate for this phenomenon. Intracellular TRACP activity can be quantitated in subpopulations of cells within mixed cell populations by flow cytofluorometry using simple cytochemical methods in combination with fluorescent antibodies to cell-surface and other differentiation antigens. The cytochemical method should be useful for basic investigations of differentiation, maturation, and function of macrophages, DCs, and osteoclasts, and for diagnosis and management of hairy cell leukemia. (J Histochem Cytochem 51:1131–1137, 2003)
Anthony J. Janckila - One of the best experts on this subject based on the ideXlab platform.
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Association of Tartrate-Resistant Acid Phosphatase-Expressed Macrophages and Metastatic Breast Cancer Progression.
Medicine, 2015Co-Authors: Yu Guang Chen, Anthony J. Janckila, Tsu Yi Chao, Ren Hua Yeh, Hong-wei Gao, Su Huei Lee, Guo Shiou Liao, Ming Shen DaiAbstract:Infiltrating neutrophils, lymphocytes, macrophages, and cytokines constitute a state of chronic inflammation within the tumor microenvironment. Tartrate-Resistant Acid Phosphatase 5a (TRACP5a) protein, a novel product of activated macrophage, is postulated to be a biomarker for systemic inflammatory burden in states of chronic inflammation. We aimed to investigate the clinical significance of TRACP5a expression in tumor-infiltrating macrophages and serum TRACP5a in patients with metastatic breast cancer (BC). We retrospectively analyzed the clinical data from 34 BC patients with confirmed skeletal/visceral metastasis upon or during first-line palliative treatment. Patients were stratified into 3 groups based on the therapeutic responses and follow-up disease course. The association of TRACP5a protein with other inflammatory and cancer biomarkers was assessed among the clinically distinct group of patients. Higher TRACP5a protein was significantly correlated with earlier disease progression and survival (P = 0.0045) in comparison to other inflammatory markers, CRP or IL-6. Patients with higher serum TRACP5a level and shorter survival and treatment refractoriness also had more TRACP+ tumor-infiltrating macrophages. Our data support a hypothesis that serum TRACP5a protein can potentially be a predictive and prognostic marker to evaluate disease progression and therapeutic response in BC patients with bone/visceral metastasis. The associations between overall survival and TRACP expression by macrophages require further prospective investigation.
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applications and performance of monoclonal antibodies to human tartrate resistant Acid Phosphatase
Journal of Immunological Methods, 2011Co-Authors: Silvia Potenziani D Pradella, Tsu Yi Chao, Lung T. Yam, Stephen P. Slone, Ranga N Parthasarathy, Anthony J. JanckilaAbstract:Abstract Background Tartrate-Resistant Acid Phosphatase (TRACP) is an enzyme common to cells of the mononuclear phagocyte system and a clinically relevant biomarker for osteoclasts and inflammatory macrophages. The purpose was to assess applications and performance of six anti-TRACP monoclonal antibodies. Methods Mab9 C5, 14 G6, 162, 203, 220, and 89 were used as capture and detection antibodies in quantitative immunoassay, and for western blot (WB), immunoprecipitation, and immunohistochemistry of paraffin sections containing chronic inflammatory infiltrates. The clinical performance of mab14 G6 for immunoassay of serum TRACP5b activity was compared to two commercial kit methods. Results Mab9 C5 is useful for WB and immunohistochemistry methods only. Mab14G6, 162, and 203 are useful for quantitative immunoassay and immunoprecipitation, however, mab203 causes inactivation of enzymatic activity. Mab220 and 89 are specific for TRACP5a and useful in all applications. Mab14G6 has similar clinical sensitivity and specificity as two commercial methods. Conclusions TRACP is an important marker in osteoimmunology. Specific antibodies with unique specificity for TRACP isoforms and defined applications will be valuable for clinical evaluation of bone metabolic, inflammatory and autoimmune diseases and will aid in basic research of TRACP biochemistry and biology.
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Applications and performance of monoclonal antibodies to human tartrate resistant Acid Phosphatase.
Journal of immunological methods, 2011Co-Authors: Silvia Potenziani D Pradella, Tsu Yi Chao, Lung T. Yam, Stephen P. Slone, Ranga N Parthasarathy, Anthony J. JanckilaAbstract:Tartrate-Resistant Acid Phosphatase (TRACP) is an enzyme common to cells of the mononuclear phagocyte system and a clinically relevant biomarker for osteoclasts and inflammatory macrophages. The purpose was to assess applications and performance of six anti-TRACP monoclonal antibodies. Mab9C5, 14G6, 162, 203, 220, and 89 were used as capture and detection antibodies in quantitative immunoassay, and for western blot (WB), immunoprecipitation, and immunohistochemistry of paraffin sections containing chronic inflammatory infiltrates. The clinical performance of mab14G6 for immunoassay of serum TRACP5b activity was compared to two commercial kit methods. Mab9C5 is useful for WB and immunohistochemistry methods only. Mab14G6, 162, and 203 are useful for quantitative immunoassay and immunoprecipitation, however, mab203 causes inactivation of enzymatic activity. Mab220 and 89 are specific for TRACP5a and useful in all applications. Mab14G6 has similar clinical sensitivity and specificity as two commercial methods. TRACP is an important marker in osteoimmunology. Specific antibodies with unique specificity for TRACP isoforms and defined applications will be valuable for clinical evaluation of bone metabolic, inflammatory and autoimmune diseases and will aid in basic research of TRACP biochemistry and biology. Published by Elsevier B.V.
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Tartrate-Resistant Acid Phosphatase as an Immunohistochemical Marker for Inflammatory Macrophages
American journal of clinical pathology, 2007Co-Authors: Anthony J. Janckila, Sheron C. Lear, Alvin W. Martin, Stephen P. Slone, Lung T. YamAbstract:Human serum contains 2 isoforms of type-5 Tartrate-Resistant Acid Phosphatase (TRACP): 5a and 5b. TRACP-5b is osteoclastic. Our goal was to determine if serum TRACP-5a could originate from inflammatory macrophages (MPhi). We stained 246 paraffin-embedded tissue samples for TRACP using monoclonal antibody 9C5 (mab9C5) to isoforms 5a and 5b and a novel mab220 specific to isoform 5a. CD68 and lysozyme were also stained. MPhi of chronic and granulomatous inflammation and in tissues that undergo strong antigenic stimulation were strongly positive for TRACP, more so with mab220 than with mab9C5. Noninflammatory MPhi in lymph node sinuses or germinal centers and red pulp MPhi of spleen were weak or negative for TRACP. Marginal zone lymphocytes and sebaceous glands of skin were weakly positive for TRACP. Tissue mast cells displayed strong TRACP staining. Neuroendocrine cells of gastrointestinal tissues were strongly immunoreactive with mab9C5 but negative with mab220. Restricted expression of TRACP primarily in inflammatory MPhi supports our hypothesis that circulating TRACP-5a could be a biomarker of chronic inflammatory disease activity.
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Development of immunoassays for serum Tartrate-Resistant Acid Phosphatase isoform 5a.
Clinica Chimica Acta, 2005Co-Authors: Tsu Yi Chao, Su Huei Lee, Lung T. Yam, David H. Neustadt, Mary M. Chen, Uzma A. Chaudhry, Anthony J. JanckilaAbstract:Abstract Background Serum Tartrate-Resistant Acid Phosphatase (TRACP) consists of 2 structurally related isoforms, TRACP 5a and 5b. TRACP 5b is from bone-resorbing osteoclasts. TRACP 5a may be a macrophage product of inflammation. We used a novel antibody to TRACP 5a to standardize immunoassays for serum TRACP 5a activity and protein. Methods Biotinylated anti-TRACP antibodies were used to immobilize serum TRACP isoforms. TRACP activity was measured using 4-nitrophenyl phosphate as substrate. TRACP 5a protein was measured with an independent peroxidase-conjugated anti-TRACP antibody. Immunoassays were standardized for linearity of serum dose response, sensitivity and precision. Reference ranges for TRACP 5a were established from serum of 50 healthy males and 50 healthy age-matched females. Serum TRACP 5a activity and protein were determined in 29 cases of rheumatoid arthritis. Results Serum matrix interference in both TRACP 5a assays required dilution to 10% serum to approach linearity. Intra-assay and inter-assay CV% were Conclusions Although TRACP 5a and 5b are related biosynthetically, their circulating levels in healthy humans were independent, suggesting differential regulation of expression. In chronic diseases, increased TRACP 5a may represent pathological processes of inflammation unrelated to bone metabolism.
Jussi M. Halleen - One of the best experts on this subject based on the ideXlab platform.
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Tartrate‐resistant Acid Phosphatase from human bone: Purification and development of an immunoassay
Journal of Bone and Mineral Research, 2009Co-Authors: Jussi M. Halleen, Jukka Hellman, Teuvo Hentunen, H. Kalervo VäänlänenAbstract:Tartrate-Resistant Acid Phosphatase (TRAP) was purified 20,000-fold to apparent homogeneity from human bone. The purified enzyme consisted of one 32 kd subunit, which was cleaved by β-mercaptoethanol into two subunits of 15 kd and 20 kd, as shown by sodium dodecyl sulfide-polyacrylamide gel electrophoresis (SDS-PAGE) and silver staining. The purified enzyme was identified by N-terminal amino Acid sequencing, and it was shown to be homologous with previously purified TRAPs from other sources. We developed a polyclonal antiserum against the purified enzyme in mice. In immunohistochemistry, the antiserum recognized osteoclasts from human bone and alveolar macrophages from human lung tissue, but no cells from human spleen tissue. It also stained osteoclasts from rat bone cells cultured on bovine bone slices. Purified TRAP could be inhibited by vanadate and molybdate, but not by tartrate, and it was activated 2-fold by β-mercaptoethanol. The glycoprotein structure of human bone TRAP was analyzed, and it was shown to contain only high-mannose type carbohydrates. We used the polyclonal antibody to develop a competitive fluorescence immunoassay for measuring serum TRAP concentrations. According to the assay, children have higher serum TRAP concentrations than adults, and postmenopausal women have higher concentrations than premenopausal women. Postmenopausal women also have higher serum TRAP concentrations than postmenopausal women on estrogen replacement therapy.
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tartrate resistant Acid Phosphatase from human bone purification and development of an immunoassay
Journal of Bone and Mineral Research, 2009Co-Authors: Jussi M. Halleen, Jukka Hellman, Teuvo Hentunen, Kalervo H VaanlanenAbstract:Tartrate-Resistant Acid Phosphatase (TRAP) was purified 20,000-fold to apparent homogeneity from human bone. The purified enzyme consisted of one 32 kd subunit, which was cleaved by β-mercaptoethanol into two subunits of 15 kd and 20 kd, as shown by sodium dodecyl sulfide-polyacrylamide gel electrophoresis (SDS-PAGE) and silver staining. The purified enzyme was identified by N-terminal amino Acid sequencing, and it was shown to be homologous with previously purified TRAPs from other sources. We developed a polyclonal antiserum against the purified enzyme in mice. In immunohistochemistry, the antiserum recognized osteoclasts from human bone and alveolar macrophages from human lung tissue, but no cells from human spleen tissue. It also stained osteoclasts from rat bone cells cultured on bovine bone slices. Purified TRAP could be inhibited by vanadate and molybdate, but not by tartrate, and it was activated 2-fold by β-mercaptoethanol. The glycoprotein structure of human bone TRAP was analyzed, and it was shown to contain only high-mannose type carbohydrates. We used the polyclonal antibody to develop a competitive fluorescence immunoassay for measuring serum TRAP concentrations. According to the assay, children have higher serum TRAP concentrations than adults, and postmenopausal women have higher concentrations than premenopausal women. Postmenopausal women also have higher serum TRAP concentrations than postmenopausal women on estrogen replacement therapy.
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tartrate resistant Acid Phosphatase 5b tracp 5b as a marker of bone resorption
Clinical Laboratory, 2006Co-Authors: Jussi M. Halleen, S L Tiitinen, Hannele Ylipahkala, Katja M Fagerlund, Kalervo H VaananenAbstract:Tartrate-Resistant Acid Phosphatase (TRACP) is an enzyme that is expressed in high amounts by bone resorbing osteoclasts, inflammatory macrophages and dendritic cells. Two forms of TRACP circulate in human blood, TRACP 5a derived from macrophages and dendritic cells, and TRACP 5b derived from osteoclasts. Recent data have demonstrated the utility of TRACP 5b as a marker of osteoclast number and bone resorption, and serum TRACP 5a as a marker of inflammatory conditions. This review summarizes the scientific knowledge on the role of TRACP in osteoclastic bone resorption, the mechanism of TRACP 5b generation in osteoclasts and its secretion into the blood circulation, the methodology of measuring TRACP 5b, diagnostic evidence for the use of TRACP 5b as a resorption marker, and characteristics of TRACP 5b compared to other commonly used bone turnover markers.
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Tartrate-Resistant Acid Phosphatase 5B circulates in human serum in complex with α2-macroglobulin and calcium
Biochemical and biophysical research communications, 2003Co-Authors: Hannele Ylipahkala, Jussi M. Halleen, Helena Kaija, Pirkko Vihko, H. Kalervo VäänänenAbstract:Abstract Tartrate-Resistant Acid Phosphatase (TRACP) is an enzyme with unknown biological function. In addition to its Acid Phosphatase activity, TRACP is capable of generating reactive oxygen species (ROS) at neutral pH. Two forms of TRACP circulate in human serum, macrophage-derived TRACP 5a and osteoclast-derived TRACP 5b. Here we have studied the circulating forms of the osteoclast-derived TRACP 5b in rat and human serum. In human serum, TRACP 5b circulates in a large complex that contained α 2 M and calcium. On the contrary, rat serum TRACP 5b circulates as a free molecule. Formation of the TRACP 5b complex in vitro decreased significantly the ROS generating activity of TRACP 5b without affecting its Phosphatase activity. These results suggest that the complex formation may be necessary to eliminate the formation of the harmful ROS in the neutral pH of serum.
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Tartrate-Resistant Acid Phosphatase 5B is a specific and sensitive marker of bone resorption.
Anticancer research, 2003Co-Authors: Jussi M. HalleenAbstract:Bone resorbing osteoclasts contain high amounts of Tartrate-Resistant Acid Phosphatase (TRACP) 5b and secrete it into the blood circulation. Circulating TRACP 5b activity is derived exclusively from osteoclasts. We have developed a TRACP 5b-specific-immunoassay using a monoclonal antibody O1A that was developed using TRACP 5b purified from human osteoclasts as antigen. Serum TRACP 5b activity has a low diurnal variability, and it does not accumulate in the circulation in renal or hepatic failure. It is elevated in 80% of patients with osteoporosis, while decreased 40-50% after antiresorptive therapy with estrogen and the bisphosphonate alendronate. Preliminary results show that serum TRACP 5b activity is normal in breast cancer patients without bone metastases, and elevated in approximately 80% of breast cancer patients with bone metastases. These results suggest that serum TRACP 5b activity may be a useful marker for the early detection of the spreading of breast cancer cells to bone.
Hans G. Drexler - One of the best experts on this subject based on the ideXlab platform.
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Biology of Tartrate-Resistant Acid Phosphatase.
Leukemia & lymphoma, 2000Co-Authors: Elke C. Lamp, Hans G. DrexlerAbstract:Tartrate-Resistant Acid Phosphatase (TRAP) is a member of the ubiquitously expressed enzyme family of the Acid Phosphatases. Nearly 30 years ago, TRAP became known to hematologists as cytochemical marker enzyme of hairy cell leukemia. Physiologically, TRAP is primarily a cytochemical marker of macrophages, osteoclasts and dendritic cells. TRAP is localized intracellularly in the lysosomal compartment. Recent data suggest also secretion of TRAP by some cell types, in particular by osteoclasts. Human, mouse and rat TRAP are biochemically well characterized. While the complete genomic sequence of TRAP has been elucidated, only limited information on the genetic details of the gene and its regulation is available. It appears that the intracellular iron content is involved in the regulation of the enzyme. The physiological substrates for this enzyme have not been identified yet and consequently the functional role of TRAP remains completely unknown, though some hypotheses have been forwarded, e.g. involvement in bone resorption and iron homeostasis (transport, metabolism). Taken together, research on the biology of TRAP has been intensive and has led to considerable progress on a number of fronts, including the cloning of the gene. Further studies are, however, still required to determine the role of TRAP in vivo.
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Cloning and characterization of the human Tartrate-Resistant Acid Phosphatase (TRAP) gene.
Leukemia, 1996Co-Authors: Elke Fleckenstein, W. G. Dirks, Dehmel U, Hans G. DrexlerAbstract:The expression and protein structure of the Tartrate-Resistant Acid Phosphatase (TRAP), an iron-containing lysosomal glycoprotein in cells of the mononuclear phagocyte system, have been analyzed extensively in the past. In some diseases, like hairy cell leukemia and Gaucher's disease, cytochemically detected TRAP expression is used as a disease-associated marker. In this paper we describe the isolation of a genomic cosmid clone of the human TRAP gene. Restriction mapping revealed a 22-kb insert and the complete genomic structure of the TRAP gene. A 6-kb HindIII-fragment harboring the entire TRAP gene was subcloned and the 5'-flanking region of 3026 bp was sequenced. Analysis of the sequence data showed the presence of potential transcription factor binding sites. Two transcriptional start sites were identified in the untranslated exon 1 at positions -349 and -347 bp relative to the translational start codon. Linked to a luciferase-encoding reporter gene the 5'-flanking region was sufficient to direct transcription in the heterologous cell line BHK-21. Treatment of the transfected cells with different modulators of the intracellular iron content showed that regulation of TRAP expression is dependent on iron. In summary, these data imply a possible functional role of the TRAP gene product either in the storage or the transport of iron.
Ming Shen Dai - One of the best experts on this subject based on the ideXlab platform.
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Prognostic significance of Tartrate-Resistant Acid Phosphatase expression in breast cancer.
Journal of Clinical Oncology, 2019Co-Authors: Ming Shen Dai, Li-jia Chen, Shun-fu TsengAbstract:e12594Background: Tartrate-Resistant Acid Phosphatase (TRAP) is a metalloproteinase-like protein that is expressed in several primary and metastatic tumors, and its expression is positively correla...
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Association of Tartrate-Resistant Acid Phosphatase-Expressed Macrophages and Metastatic Breast Cancer Progression.
Medicine, 2015Co-Authors: Yu Guang Chen, Anthony J. Janckila, Tsu Yi Chao, Ren Hua Yeh, Hong-wei Gao, Su Huei Lee, Guo Shiou Liao, Ming Shen DaiAbstract:Infiltrating neutrophils, lymphocytes, macrophages, and cytokines constitute a state of chronic inflammation within the tumor microenvironment. Tartrate-Resistant Acid Phosphatase 5a (TRACP5a) protein, a novel product of activated macrophage, is postulated to be a biomarker for systemic inflammatory burden in states of chronic inflammation. We aimed to investigate the clinical significance of TRACP5a expression in tumor-infiltrating macrophages and serum TRACP5a in patients with metastatic breast cancer (BC). We retrospectively analyzed the clinical data from 34 BC patients with confirmed skeletal/visceral metastasis upon or during first-line palliative treatment. Patients were stratified into 3 groups based on the therapeutic responses and follow-up disease course. The association of TRACP5a protein with other inflammatory and cancer biomarkers was assessed among the clinically distinct group of patients. Higher TRACP5a protein was significantly correlated with earlier disease progression and survival (P = 0.0045) in comparison to other inflammatory markers, CRP or IL-6. Patients with higher serum TRACP5a level and shorter survival and treatment refractoriness also had more TRACP+ tumor-infiltrating macrophages. Our data support a hypothesis that serum TRACP5a protein can potentially be a predictive and prognostic marker to evaluate disease progression and therapeutic response in BC patients with bone/visceral metastasis. The associations between overall survival and TRACP expression by macrophages require further prospective investigation.
