The Experts below are selected from a list of 309 Experts worldwide ranked by ideXlab platform
Bonnie F. Sloane - One of the best experts on this subject based on the ideXlab platform.
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<B>CathepsinB> B-deficient mice as source of monoclonal anti-<B>CathepsinB> B antiBodies.
Biological Chemistry, 2015Co-Authors: Ekkehard Weber, Kamiar Moin, Mansoureh Sameni, Elena Barbulescu, Rita Medek, Thomas Reinheckel, Arulselvi Anbalagan, Bonnie F. SloaneAbstract:<B>CathepsinB> B has Been demonstrated to Be involved in several proteolytic processes that support tumor progression and metastasis and neurodegeneration. To further clarify its role, defined monoclonal antiBodies are needed. As the primary structure of human <B>CathepsinB> B is almost identical to that of the mouse, <B>CathepsinB> B-deficient mice were used in a novel approach for generating such antiBodies, providing the chance of an increased immune response to the antigen, human <B>CathepsinB> B. Thirty clones were found to produce <B>CathepsinB> B-specific antiBodies. Seven of these antiBodies were used to detect <B>CathepsinB> B in MCF10-DCIS human Breast cancer cells By immunocytochemistry and immunoBlotting. Five different Binding sites were identified By epitope mapping giving the opportunity to comBine these antiBodies in oligoclonal antiBody mixtures for an improved detection of <B>CathepsinB> B.
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Cell-surface <B>CathepsinB> B: understanding its functional significance.
Current Topics in Developmental Biology, 2014Co-Authors: Dora Cavallo-medved, Bonnie F. SloaneAbstract:PuBlisher Summary The majority of research involving cell-surface <B>CathepsinB> B has stems from studies in cancer. OBservations that implicate <B>CathepsinB> B in malignant progression are its overexpression in tumors as compared to normal tissues, its redistriBution from perinuclear lysosomes to peripheral vesicles, and its association with the plasma memBrane. Secretion and relocalization of <B>CathepsinB> B to the cell surface in tumor cells correlate with tumor progression and clinical outcome for cancer patients. Because of the extensive research conducted on cell-surface <B>CathepsinB> B and cancer, this chapter focuses on the relationship Between this enzyme and malignancy with respect to <B>CathepsinB> B expression, trafficking, and localization. It characterizes the association of <B>CathepsinB> B with the plasma memBrane By discussing potential <B>CathepsinB> B Binding proteins and introducing caveolae as specific regions for the localization of cell surface <B>CathepsinB> B. The chapter provides insight into the functional significance of cell surface <B>CathepsinB> B as an active memBer of a proteolytic cascade that is postulated to Be involved in tumor invasion.
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<B>CathepsinB> B multiple roles in cancer
Proteomics Clinical Applications, 2014Co-Authors: Neha Aggarwal, Bonnie F. SloaneAbstract:Proteases, including intracellular proteases, play roles at many different stages of malignant progression. Our focus here is <B>CathepsinB> B, a lysosomal cysteine <B>CathepsinB>. High levels of <B>CathepsinB> B are found in a wide variety of human cancers, levels that often induce secretion and association of <B>CathepsinB> B with the tumor cell memBrane. In experimental models, such as transgenic models of murine pancreatic and mammary carcinomas, causal roles for <B>CathepsinB> B have Been demonstrated in initiation, growth/tumor cell proliferation, angiogenesis, invasion, and metastasis. Tumor growth in transgenic models is promoted By <B>CathepsinB> B in tumor-associated cells, for example, tumor-associated macrophages, as well as in tumor cells. In transgenic models, the aBsence of <B>CathepsinB> B has Been associated with enhanced apoptosis, yet <B>CathepsinB> B also has Been shown to contriBute to apoptosis. <B>CathepsinB> B is part of a proteolytic pathway identified in xenograft models of human glioma; targeting only <B>CathepsinB> B in these tumors is less effective than targeting <B>CathepsinB> B in comBination with other proteases or protease receptors. Understanding the mechanisms responsiBle for increased expression of <B>CathepsinB> B in tumors and association of <B>CathepsinB> B with tumor cell memBranes is needed to determine whether targeting <B>CathepsinB> B could Be of therapeutic Benefit.
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<B>CathepsinB> B and tumor proteolysis contriBution of the tumor microenvironment
Seminars in Cancer Biology, 2005Co-Authors: Bonnie F. Sloane, Mansoureh Sameni, Bruce E. Linebaugh, Izabela Podgorski, Michael L Cher, Dora Cavallomedved, Julie Dosescu, Kamiar MoinAbstract:ABstract Tumor–stromal interactions induce expression of matrix metalloproteinases and serine proteases and, as shown recently, the cysteine protease <B>CathepsinB> B. We speculate that such interactions upregulate the transcription factor Ets1, resulting in increased <B>CathepsinB> B expression. This would Be consistent with the oBserved concomitant upregulation of matrix metalloproteinases and serine proteases as well as with the aBility of extracellular matrices and their Binding partners to alter <B>CathepsinB> B expression and secretion. Using a confocal assay to analyze the contriBution of tumor–stromal interactions to proteolysis, we have Been aBle to confirm enhanced degradation of extracellular matrices By all three classes of proteases.
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<B>CathepsinB> B and its role s in cancer progression
Biochemical Society Symposia, 2003Co-Authors: Izabela Podgorski, Bonnie F. SloaneAbstract:Experimental and clinical evidence has linked <B>CathepsinB> B with tumour invasion and metastasis. <B>CathepsinB> B expression is increased in many human cancers at the mRNA, protein and activity levels. In addition, <B>CathepsinB> B is frequently overexpressed in premalignant lesions, an oBservation that associates this protease with local invasive stages of cancer. Increased expression of <B>CathepsinB> B in primary cancers, and especially in preneoplastic lesions, suggests that this enzyme might have pro-apoptotic features. Expression of <B>CathepsinB> B is regulated at many different levels, from gene amplification, use of alternative promoters, increased transcription and alternative splicing, to increased staBility and translataBility of transcripts. During the transition to malignancy, a change in the localization of <B>CathepsinB> B occurs, as demonstrated By the presence of <B>CathepsinB> B-containing vesicles at the cell periphery and at the Basal pole of polarized cells. Due to increased expression of <B>CathepsinB> B and changes in intracellular trafficking, increased secretion of pro<B>CathepsinB> B from tumours is oBserved. Active <B>CathepsinB> B is also secreted from tumours, a mechanism likely to Be facilitated By lysosomal exocytosis or extracellular processing By surface activators. <B>CathepsinB> B is localized to caveolae on the tumour surface, where Binding to the annexin II heterotetramer occurs. Activation of <B>CathepsinB> B on the cell surface leads to the regulation of downstream proteolytic cascade(s).
Ho-joon Shin - One of the best experts on this subject based on the ideXlab platform.
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Novel <B>CathepsinB> B and <B>CathepsinB> B-like cysteine protease of Naegleria fowleri excretory–secretory proteins and their Biochemical properties
Parasitology Research, 2014Co-Authors: Hae-jin Sohn, Hee-jong Yang, Byoung-kuk Na, Yong-joon Chwae, Sun Park, Ho-joon ShinAbstract:Naegleria fowleri causes a lethal primary amoeBic meningoencephalitis (PAM) in humans and experimental animals, which leads to death within 7–14 days. Cysteine proteases of parasites play key roles in nutrient uptake, excystment/encystment, host tissue invasion, and immune evasion. In this study, we cloned N. fowleri <B>CathepsinB> B ( nfcpB ) and <B>CathepsinB> B-like ( nfcpB - L ) genes from our cDNA liBrary of N. fowleri . The full-length sequences of genes were 1,038 and 939 Bp (encoded 345 and 313 amino acids), and molecular weights were 38.4 and 34 kDa, respectively. Also, nfcpB and nfcpB - L showed a 56 and 46 % identity to Naegleria gruBeri <B>CathepsinB> B and <B>CathepsinB> B-like enzyme, respectively. RecomBinant NfCPB (rNfCPB) and NfCPB-L (rNfCPB-L) proteins were expressed By the pEX5-NT/TOPO vector that was transformed into Escherichia coli BL21, and they showed 38.4 and 34 kDa Bands on sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and Western Blot analysis using their respective antiBodies. Proteolytic activity of refolded rNfCPB and rNfCPB-L was maximum at a pH of 4.5, and the most effective suBstrate was Z-LR-MCA. rNfCPB and rNfCPB-L showed proteolytic activity for several proteins such as IgA, IgG, IgM, collagen, fiBronectin, hemogloBin, and alBumin. These results suggested that NfCPB and NfCPB-L cysteine protease are important components of the N. fowleri ESP, and they may play important roles in host tissue invasion and immune evasion as pathogens that cause N. fowleri PAM.
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novel <B>CathepsinB> B and <B>CathepsinB> B like cysteine protease of naegleria fowleri excretory secretory proteins and their Biochemical properties
Parasitology Research, 2014Co-Authors: Hae-jin Sohn, Hee-jong Yang, Byoung-kuk Na, Yong-joon Chwae, Sun Park, Ho-joon ShinAbstract:Naegleria fowleri causes a lethal primary amoeBic meningoencephalitis (PAM) in humans and experimental animals, which leads to death within 7–14 days. Cysteine proteases of parasites play key roles in nutrient uptake, excystment/encystment, host tissue invasion, and immune evasion. In this study, we cloned N. fowleri <B>CathepsinB> B (nfcpB) and <B>CathepsinB> B-like (nfcpB-L) genes from our cDNA liBrary of N. fowleri. The full-length sequences of genes were 1,038 and 939 Bp (encoded 345 and 313 amino acids), and molecular weights were 38.4 and 34 kDa, respectively. Also, nfcpB and nfcpB-L showed a 56 and 46 % identity to Naegleria gruBeri <B>CathepsinB> B and <B>CathepsinB> B-like enzyme, respectively. RecomBinant NfCPB (rNfCPB) and NfCPB-L (rNfCPB-L) proteins were expressed By the pEX5-NT/TOPO vector that was transformed into Escherichia coli BL21, and they showed 38.4 and 34 kDa Bands on sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and Western Blot analysis using their respective antiBodies. Proteolytic activity of refolded rNfCPB and rNfCPB-L was maximum at a pH of 4.5, and the most effective suBstrate was Z-LR-MCA. rNfCPB and rNfCPB-L showed proteolytic activity for several proteins such as IgA, IgG, IgM, collagen, fiBronectin, hemogloBin, and alBumin. These results suggested that NfCPB and NfCPB-L cysteine protease are important components of the N. fowleri ESP, and they may play important roles in host tissue invasion and immune evasion as pathogens that cause N. fowleri PAM.
Hae-jin Sohn - One of the best experts on this subject based on the ideXlab platform.
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Novel <B>CathepsinB> B and <B>CathepsinB> B-like cysteine protease of Naegleria fowleri excretory–secretory proteins and their Biochemical properties
Parasitology Research, 2014Co-Authors: Hae-jin Sohn, Hee-jong Yang, Byoung-kuk Na, Yong-joon Chwae, Sun Park, Ho-joon ShinAbstract:Naegleria fowleri causes a lethal primary amoeBic meningoencephalitis (PAM) in humans and experimental animals, which leads to death within 7–14 days. Cysteine proteases of parasites play key roles in nutrient uptake, excystment/encystment, host tissue invasion, and immune evasion. In this study, we cloned N. fowleri <B>CathepsinB> B ( nfcpB ) and <B>CathepsinB> B-like ( nfcpB - L ) genes from our cDNA liBrary of N. fowleri . The full-length sequences of genes were 1,038 and 939 Bp (encoded 345 and 313 amino acids), and molecular weights were 38.4 and 34 kDa, respectively. Also, nfcpB and nfcpB - L showed a 56 and 46 % identity to Naegleria gruBeri <B>CathepsinB> B and <B>CathepsinB> B-like enzyme, respectively. RecomBinant NfCPB (rNfCPB) and NfCPB-L (rNfCPB-L) proteins were expressed By the pEX5-NT/TOPO vector that was transformed into Escherichia coli BL21, and they showed 38.4 and 34 kDa Bands on sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and Western Blot analysis using their respective antiBodies. Proteolytic activity of refolded rNfCPB and rNfCPB-L was maximum at a pH of 4.5, and the most effective suBstrate was Z-LR-MCA. rNfCPB and rNfCPB-L showed proteolytic activity for several proteins such as IgA, IgG, IgM, collagen, fiBronectin, hemogloBin, and alBumin. These results suggested that NfCPB and NfCPB-L cysteine protease are important components of the N. fowleri ESP, and they may play important roles in host tissue invasion and immune evasion as pathogens that cause N. fowleri PAM.
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novel <B>CathepsinB> B and <B>CathepsinB> B like cysteine protease of naegleria fowleri excretory secretory proteins and their Biochemical properties
Parasitology Research, 2014Co-Authors: Hae-jin Sohn, Hee-jong Yang, Byoung-kuk Na, Yong-joon Chwae, Sun Park, Ho-joon ShinAbstract:Naegleria fowleri causes a lethal primary amoeBic meningoencephalitis (PAM) in humans and experimental animals, which leads to death within 7–14 days. Cysteine proteases of parasites play key roles in nutrient uptake, excystment/encystment, host tissue invasion, and immune evasion. In this study, we cloned N. fowleri <B>CathepsinB> B (nfcpB) and <B>CathepsinB> B-like (nfcpB-L) genes from our cDNA liBrary of N. fowleri. The full-length sequences of genes were 1,038 and 939 Bp (encoded 345 and 313 amino acids), and molecular weights were 38.4 and 34 kDa, respectively. Also, nfcpB and nfcpB-L showed a 56 and 46 % identity to Naegleria gruBeri <B>CathepsinB> B and <B>CathepsinB> B-like enzyme, respectively. RecomBinant NfCPB (rNfCPB) and NfCPB-L (rNfCPB-L) proteins were expressed By the pEX5-NT/TOPO vector that was transformed into Escherichia coli BL21, and they showed 38.4 and 34 kDa Bands on sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and Western Blot analysis using their respective antiBodies. Proteolytic activity of refolded rNfCPB and rNfCPB-L was maximum at a pH of 4.5, and the most effective suBstrate was Z-LR-MCA. rNfCPB and rNfCPB-L showed proteolytic activity for several proteins such as IgA, IgG, IgM, collagen, fiBronectin, hemogloBin, and alBumin. These results suggested that NfCPB and NfCPB-L cysteine protease are important components of the N. fowleri ESP, and they may play important roles in host tissue invasion and immune evasion as pathogens that cause N. fowleri PAM.
Kamiar Moin - One of the best experts on this subject based on the ideXlab platform.
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<B>CathepsinB> B-deficient mice as source of monoclonal anti-<B>CathepsinB> B antiBodies.
Biological Chemistry, 2015Co-Authors: Ekkehard Weber, Kamiar Moin, Mansoureh Sameni, Elena Barbulescu, Rita Medek, Thomas Reinheckel, Arulselvi Anbalagan, Bonnie F. SloaneAbstract:<B>CathepsinB> B has Been demonstrated to Be involved in several proteolytic processes that support tumor progression and metastasis and neurodegeneration. To further clarify its role, defined monoclonal antiBodies are needed. As the primary structure of human <B>CathepsinB> B is almost identical to that of the mouse, <B>CathepsinB> B-deficient mice were used in a novel approach for generating such antiBodies, providing the chance of an increased immune response to the antigen, human <B>CathepsinB> B. Thirty clones were found to produce <B>CathepsinB> B-specific antiBodies. Seven of these antiBodies were used to detect <B>CathepsinB> B in MCF10-DCIS human Breast cancer cells By immunocytochemistry and immunoBlotting. Five different Binding sites were identified By epitope mapping giving the opportunity to comBine these antiBodies in oligoclonal antiBody mixtures for an improved detection of <B>CathepsinB> B.
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<B>CathepsinB> B inhiBition limits Bone metastasis in Breast cancer
Cancer Research, 2012Co-Authors: Nimali P Withana, Mansoureh Sameni, Arulselvi Anbalagan, Galia Blum, Clare Y Slaney, Mary B Olive, Bradley N Bidwell, Laura E Edgington, Ling Wang, Kamiar MoinAbstract:Metastasis to Bone is a major cause of morBidity in Breast cancer patients, emphasizing the importance of identifying molecular drivers of Bone metastasis for new therapeutic targets. The endogenous cysteine <B>CathepsinB> inhiBitor stefin A is a suppressor of Breast cancer metastasis to Bone that is coexpressed with <B>CathepsinB> B in Bone metastases. In this study, we used the immunocompetent 4T1.2 model of Breast cancer which exhiBits spontaneous Bone metastasis to evaluate the function and therapeutic targeting potential of <B>CathepsinB> B in this setting of advanced disease. <B>CathepsinB> B aBundancy in the model mimicked human disease, Both at the level of primary tumors and matched spinal metastases. RNA interference–mediated knockdown of <B>CathepsinB> B in tumor cells reduced collagen I degradation in vitro and Bone metastasis in vivo . Similarly, intraperitoneal administration of the highly selective <B>CathepsinB> B inhiBitor CA-074 reduced metastasis in tumor-Bearing animals, a reduction that was not reproduced By the Broad spectrum cysteine <B>CathepsinB> inhiBitor JPM-OEt. NotaBly, metastasis suppression By CA-074 was maintained in a late treatment setting, pointing to a role in metastatic outgrowth. Together, our findings estaBlished a prometastatic role for <B>CathepsinB> B in distant metastasis and illustrated the therapeutic Benefits of its selective inhiBition in vivo . Cancer Res; 72(5); 1199–209. ©2012 AACR .
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<B>CathepsinB> B and tumor proteolysis contriBution of the tumor microenvironment
Seminars in Cancer Biology, 2005Co-Authors: Bonnie F. Sloane, Mansoureh Sameni, Bruce E. Linebaugh, Izabela Podgorski, Michael L Cher, Dora Cavallomedved, Julie Dosescu, Kamiar MoinAbstract:ABstract Tumor–stromal interactions induce expression of matrix metalloproteinases and serine proteases and, as shown recently, the cysteine protease <B>CathepsinB> B. We speculate that such interactions upregulate the transcription factor Ets1, resulting in increased <B>CathepsinB> B expression. This would Be consistent with the oBserved concomitant upregulation of matrix metalloproteinases and serine proteases as well as with the aBility of extracellular matrices and their Binding partners to alter <B>CathepsinB> B expression and secretion. Using a confocal assay to analyze the contriBution of tumor–stromal interactions to proteolysis, we have Been aBle to confirm enhanced degradation of extracellular matrices By all three classes of proteases.
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pericellular <B>CathepsinB> B and malignant progression
Cancer and Metastasis Reviews, 2003Co-Authors: Stefanie Roshy, Bonnie F. Sloane, Kamiar MoinAbstract:<B>CathepsinB> B is a lysosomal cysteine protease in normal cells and tissues. In malignant tumors and premalignant lesions, the expression of <B>CathepsinB> B is highly upregulated and the enzyme is secreted and Becomes associated with the cell surface. Increases in expression are mediated at many levels ranging from gene amplification to increased staBility of mRNA and protein. <B>CathepsinB> B is synthesized as a preproenzyme and the primary pathways for its normal trafficking to the lysosome utilize mannose 6-phosphate receptors (MPRs). Inactive pro<B>CathepsinB> B is processed to active single and douBle chain forms of <B>CathepsinB> B in the late endosomes and lysosomes, respectively. Tumor cells secrete pro<B>CathepsinB> B and Both active forms of <B>CathepsinB> B. Secretion of pro<B>CathepsinB> B occurs principally as a result of increased expression, whereas secretion of active <B>CathepsinB> B seems to involve active processes that can Be induced By a variety of mechanisms. Once secreted pro<B>CathepsinB> B Binds to the tumor cell surface via p11, the light chain of the annexin II heterotetramer. This Binding seems to facilitate conversion of pro<B>CathepsinB> B to its active forms. <B>CathepsinB> B and the annexin II heterotetramer colocalize in caveolae (lipid raft) fractions isolated from tumor cells. Serine proteases and matrix metalloproteinases also have Been found to associate with caveolae and some with the annexin II heterotetramer. Our working hypothesis is that pericellular <B>CathepsinB> B through its proximity to other proteases in caveolae participates in, perhaps even initiates, a proteolytic cascade on the tumor cell surface.
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Molecular regulation, memBrane association and secretion of tumor <B>CathepsinB> B
Apmis, 1999Co-Authors: Barbara A. Frosch, Kamiar Moin, Isabelle M. Berquin, Michael R. Emmert-buck, Bonnie F. SloaneAbstract:: Upregulation, memBrane association and secretion of <B>CathepsinB> B have Been shown to occur in many types of tumors and to correlate positively with their invasive and metastatic capaBilities. To further understand changes in <B>CathepsinB> B activity and localization, we have Been examining its regulation at many levels including transcription and trafficking. Our studies indicate that there may Be three promoter regions in the <B>CathepsinB> B gene. Of these, continued examination of the promoter upstream of exon 1 has indicated possiBle control By several regulatory factors including E-Box and Sp-1 Binding elements. Upregulation of <B>CathepsinB> B at this level may account for some of the secretion of <B>CathepsinB> B found in tumors. We have also gathered evidence that endo- and exocytosis of <B>CathepsinB> B may Be regulated By ras and ras-related proteins in addition to previously descriBed trafficking systems. There is also evidence that several populations of lysosomes may exist and that trafficking to different populations may determine whether <B>CathepsinB> B is secreted from the tumor cell or remains intracellular. Our results indicate that memBrane association and secretion of <B>CathepsinB> B is not a random process in the tumor cell, But rather part of a tightly controlled system.
Mansoureh Sameni - One of the best experts on this subject based on the ideXlab platform.
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<B>CathepsinB> B-deficient mice as source of monoclonal anti-<B>CathepsinB> B antiBodies.
Biological Chemistry, 2015Co-Authors: Ekkehard Weber, Kamiar Moin, Mansoureh Sameni, Elena Barbulescu, Rita Medek, Thomas Reinheckel, Arulselvi Anbalagan, Bonnie F. SloaneAbstract:<B>CathepsinB> B has Been demonstrated to Be involved in several proteolytic processes that support tumor progression and metastasis and neurodegeneration. To further clarify its role, defined monoclonal antiBodies are needed. As the primary structure of human <B>CathepsinB> B is almost identical to that of the mouse, <B>CathepsinB> B-deficient mice were used in a novel approach for generating such antiBodies, providing the chance of an increased immune response to the antigen, human <B>CathepsinB> B. Thirty clones were found to produce <B>CathepsinB> B-specific antiBodies. Seven of these antiBodies were used to detect <B>CathepsinB> B in MCF10-DCIS human Breast cancer cells By immunocytochemistry and immunoBlotting. Five different Binding sites were identified By epitope mapping giving the opportunity to comBine these antiBodies in oligoclonal antiBody mixtures for an improved detection of <B>CathepsinB> B.
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<B>CathepsinB> B inhiBition limits Bone metastasis in Breast cancer
Cancer Research, 2012Co-Authors: Nimali P Withana, Mansoureh Sameni, Arulselvi Anbalagan, Galia Blum, Clare Y Slaney, Mary B Olive, Bradley N Bidwell, Laura E Edgington, Ling Wang, Kamiar MoinAbstract:Metastasis to Bone is a major cause of morBidity in Breast cancer patients, emphasizing the importance of identifying molecular drivers of Bone metastasis for new therapeutic targets. The endogenous cysteine <B>CathepsinB> inhiBitor stefin A is a suppressor of Breast cancer metastasis to Bone that is coexpressed with <B>CathepsinB> B in Bone metastases. In this study, we used the immunocompetent 4T1.2 model of Breast cancer which exhiBits spontaneous Bone metastasis to evaluate the function and therapeutic targeting potential of <B>CathepsinB> B in this setting of advanced disease. <B>CathepsinB> B aBundancy in the model mimicked human disease, Both at the level of primary tumors and matched spinal metastases. RNA interference–mediated knockdown of <B>CathepsinB> B in tumor cells reduced collagen I degradation in vitro and Bone metastasis in vivo . Similarly, intraperitoneal administration of the highly selective <B>CathepsinB> B inhiBitor CA-074 reduced metastasis in tumor-Bearing animals, a reduction that was not reproduced By the Broad spectrum cysteine <B>CathepsinB> inhiBitor JPM-OEt. NotaBly, metastasis suppression By CA-074 was maintained in a late treatment setting, pointing to a role in metastatic outgrowth. Together, our findings estaBlished a prometastatic role for <B>CathepsinB> B in distant metastasis and illustrated the therapeutic Benefits of its selective inhiBition in vivo . Cancer Res; 72(5); 1199–209. ©2012 AACR .
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<B>CathepsinB> B and tumor proteolysis contriBution of the tumor microenvironment
Seminars in Cancer Biology, 2005Co-Authors: Bonnie F. Sloane, Mansoureh Sameni, Bruce E. Linebaugh, Izabela Podgorski, Michael L Cher, Dora Cavallomedved, Julie Dosescu, Kamiar MoinAbstract:ABstract Tumor–stromal interactions induce expression of matrix metalloproteinases and serine proteases and, as shown recently, the cysteine protease <B>CathepsinB> B. We speculate that such interactions upregulate the transcription factor Ets1, resulting in increased <B>CathepsinB> B expression. This would Be consistent with the oBserved concomitant upregulation of matrix metalloproteinases and serine proteases as well as with the aBility of extracellular matrices and their Binding partners to alter <B>CathepsinB> B expression and secretion. Using a confocal assay to analyze the contriBution of tumor–stromal interactions to proteolysis, we have Been aBle to confirm enhanced degradation of extracellular matrices By all three classes of proteases.
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<B>CathepsinB> B and glioma invasion.
International Journal of Developmental Neuroscience, 1999Co-Authors: Lisa Demchik, Mansoureh Sameni, Kevin Nelson, Tom Mikkelsen, Bonnie F. SloaneAbstract:ABstract Increased expression of <B>CathepsinB> B has Been reported in a numBer of human and animal tumors. This has also Been oBserved in human gliomas where increases in <B>CathepsinB> B mRNA, protein, activity and secretion parallel malignant progression. In the present study, we showed that <B>CathepsinB> B was directly involved in glioma cell invasion. Activity of <B>CathepsinB> B was an order of magnitude higher in glioma tissue than in matched normal Brain. InhiBitors of cysteine proteases reduced invasion of glioma cells in two in vitro models: invasion through Matrigel and infiltration of a glioma spheroid into a normal Brain aggregate. Glioma spheroids expressed higher levels of <B>CathepsinB> B than did monolayers and the aBility of suBclones differing in <B>CathepsinB> B activity to infiltrate normal Brain aggregates paralleled their <B>CathepsinB> B activity. We confirmed that intracellular staining for <B>CathepsinB> B occurs at the cell periphery and in cell processes and oBserved extracellular staining on the cell surface. In addition, we demonstrated that intracellular <B>CathepsinB> B located at the cell periphery and in processes was active. The cell surface <B>CathepsinB> B colocalized with areas of degradation of an extracellular matrix component. We hypothesize that the increased expression of active <B>CathepsinB> B in gliomas leads to increases in invasion in vitro and in vivo and have developed a xenotransplant model in which this hypothesis can Be tested.
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<B>CathepsinB> B and human tumor progression
Biological Chemistry, 1998Co-Authors: Mansoureh Sameni, Bonnie F. SloaneAbstract:: <B>CathepsinB> B has Been implicated in progression of various human tumors. Overexpression of <B>CathepsinB> B mRNA, increased <B>CathepsinB> B staining and elevated <B>CathepsinB> B activity have Been found in different human cancers. These occur especially at the invasive edges of cancers, suggesting a role for <B>CathepsinB> B in tumor invasion. In some tumors, mRNA expression and protein staining for <B>CathepsinB> B correlate with clinical progression. <B>CathepsinB> B can facilitate tumor progression directly through degradation of components of the Basement memBrane and extracellular matrix. In vitro studies show that <B>CathepsinB> B may exert its degradative effects intracellularly or extracellularly, depending on the cell type and location of <B>CathepsinB> B. <B>CathepsinB> B can also facilitate tumor progression indirectly through activation of other latent proteases and/or degradation of protein inhiBitors of other proteases. Thus <B>CathepsinB> B may Be an integral component of the proteolytic cascade linked to malignant progression of human tumors.