Immunohistochemical demonstration of cathepsin B in the macrophages of benign and malignant lymphoid tissues

Crocker, J; Burnett, David; Jones, E. L.

doi:10.1002/path.1711420114

Cited by 41 publications

(17 citation statements)

References 22 publications

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“…Because of their proposed role in intracellular protein degradation, cysteine endopeptidases are expected to be present in all tissues containing lysosomes. By immunochemistry and immunoassay, cathepsins B and L have been demonstrated in human lymph nodes, kidney, spleen, liver, lung, brain, gastrointestinal tissues, heart and skeletal muscle (Crocker and Burnett, 1984;Howie and Burnett, 1985). However, quantitative comparisons of enzyme specific activity levels for cathepsins B and L over this range of human tissues have not yet been reported.…”

Section: Cysteine Endopeptidase Activity Levels In Normal Human Tissusupporting

confidence: 91%

Cysteine endopeptidase activity levels in normal human tissues, colorectal adenomas and carcinomas

Shuja¹,

Sheahan

Murnane³

1991

Intl Journal of Cancer

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We have assayed cysteine endopeptidase activities in 17 types of normal human tissue and in matched sets of colorectal mucosa, adenoma and carcinoma samples. Our data indicate that cathepsin B enzyme levels vary 70-fold and cathepsin L enzyme levels vary 20-fold from one normal tissue to another. Cathepsin B specific activity in normal tissues fell into 3 categories. High activity, with a mean of 156.7 +/- 41.5 nmoles min-1 mg-1 protein, was measured in liver, thyroid, kidney and spleen; intermediate activity, with a mean of 60.2 +/- 8.3 nmoles min-1 mg-1 protein, was measured in heart, colon, adrenal and lung; and low activity, with a mean of 18.4 +/- 9.7 nmoles min-1 mg-1 protein, was measured in prostate, testis, nerve, stomach, pancreas, brain, skeletal muscle, skin and breast. Cathepsin L specific activity fell into 2 categories. High activity, with a mean of 51.1 +/- 4.9 nmoles min-1 mg-1 protein, was measured in thyroid, liver and kidney; and low activity, with a mean of 11.4 +/- 5.5 nmoles min-1 mg-1 protein, was measured in spleen, colon, heart, adrenal, lung, testis, brain, nerve, skin, stomach, pancreas, skeletal muscle, prostate and breast. Our characterization of these enzyme levels provides a reference standard for normal cathepsin B and L activities in human tissues that should enhance the detection of their deregulation in disease states. For example, in studies of colorectal carcinoma and normal mucosa, we observed a significant tumor-specific increase in cathepsin B and L activities with particularly high activity levels in earlier (Dukes' A and B) compared to later (Dukes' C and D) stages of colorectal cancer. In contrast, adenomas from colorectal cancer patients expressed normal levels of cathepsin B activity, providing evidence that the increase in expression of cathepsin B may be a sensitive marker for progression from the pre-malignant to the malignant state in the development of colorectal cancer.

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Section: Cysteine Endopeptidase Activity Levels In Normal Human Tissusupporting

confidence: 91%

Cysteine endopeptidase activity levels in normal human tissues, colorectal adenomas and carcinomas

Shuja¹,

Sheahan

Murnane³

1991

Intl Journal of Cancer

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“…In the present investigation, a panel of monoclonal and polyclonal antibodies was exploited to identify the nature of these cells. The foam cells were found to be consistently and intensely stained for cathepsin B, a marker for macrophages (24). These findings support the origin of foam cells as cells of the monocyte/macrophage lineage.…”

Section: Discussionsupporting

confidence: 69%

Characterization of verruciform xanthoma by in situ hybridization and immunohistochemistry

Iamaroon

Vickers

1996

J Oral Pathology Medicine

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Verruciform xanthoma (VX) is a rare, benign lesion, mainly found in the oral mucosa. Histologically and ultrastructurally, the lesion is characteristic and well defined. However, the etiology of the lesion remains unclear. The purpose of the present study was to elaborate upon the pathogenesis of VX by evaluation of an additional series of oral examples for human papillomaviruses (HPV), using immunohistochemistry and in situ hybridization, and to further characterize the cellular components of VX immunohistochemically. Twelve specimens diagnosed as VX were retrospectively collected. One of the twelve specimens was positive for HPV types 6/11 by in situ hybridization. None of the twelve specimens demonstrated the presence of HPV antigen by immunohistochemistry. By immunohistochemical studies, the predominant cells in the inflammatory infiltrate were T cells. The foam cells were of monocyte/macrophage lineage. S-100-positive (Langerhans) cells were occasionally found in the suprabasal layer of the epithelium. HLA-DR-positive keratinocytes were noted at the intense inflammatory sites. Taken together, these findings suggest that an immune response may play a role, at least in part, in VX pathogenesis.

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“…This is also supported by expression of a third member of this family of enzymes, cathepsin B, on many HRS cells in HL tissue. 54 For both cathepsin B and S, an important role in tumor progression has been reported (reviewed by Gocheva and Joyce 55 ). Cathepsin B or S deficiency impaired both angiogenesis and tumor cell proliferation in an animal model.…”

Section: Discussionmentioning

confidence: 99%

Proteomics analysis of Hodgkin lymphoma: identification of new players involved in the cross-talk between HRS cells and infiltrating lymphocytes

Yue¹,

Visser²,

Roelofsen³

et al. 2008

Blood

118

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IntroductionHodgkin lymphoma (HL) is characterized by a minority of neoplastic cells, the Hodgkin and Reed-Sternberg cells (HRS cells), and an extensive inflammatory background. Many studies have documented that HL is associated with disturbed cytokine production. 1 Cytokine and chemokine production may not only promote growth of HRS cells and help to evade immune surveillance, but also cause the characteristic histology and the clinical symptoms of HL. 2 Cross-talk between HRS cells and surrounding lymphocytes has been studied for many years, and this interaction is regarded to be important for the pathogenesis of HL.The application of proteomics techniques has been proven to be a powerful tool for the identification of new biomarkers involved in pathogenesis of many diseases (reviewed by Hanash 3 ). Some studies on hematologic malignancies using proteomics approaches have been reported, 4,5 but application of proteomics technology to HL is still limited. Fujii et al compared HL cell line proteome to anaplastic large cell lymphoma (ALCL) and non-Hodgkin lymphoma (NHL) using a 2-dimensional difference gel electrophoresis approach of total cell lysates. 6,7 HL expressed higher levels of pyridoxine-5Ј-phosphate oxidase, vinculin, dihydropyrimidinase-related protein-2 and NADHubiquinone oxidoreductase compared with ALCL. In comparison to NHL cell lines, HL cell lines showed higher expression of pyridoxine-5Ј-phosphate oxidase, ␥-enolase, vinculin, vimentin, galectin-1, annexin A5, and protein kinase C substrate. 7 Carvalho et al identified changes in the spectrum using quadrupole-time-of-flight hybrid mass spectrometer in serum of HL patients compared with normal controls, but no further protein identification was performed. 8 Overall, only very limited proteomics data are available for HL.To gain more insight into the proteins secreted by HRS cells that might be involved in the cross-talk with infiltrating lymphocytes or might serve as tumor biomarkers, the secretome of HL cell lines was determined in cell culture supernatant. Protein identification was performed by nanoscale reversed-phase liquid chromatography tandem mass spectrometry (LC-MS/MS) after 1D-SDS-PAGE fractionation. Proteins related to immune response were validated in cell culture supernatant and patient plasma by enzyme-linked immunosorbent assay (ELISA) and in tumor tissues by immunohistochemistry. Methods Cell lines and cultureThe HL cell lines L1236 and KMH2 were established from HL patients with mixed cellularity subtype, L428 from nodular sclerosis subtype and DEV from nodular lymphocyte predominant HL (NLPHL) subtype. They were cultured in RPMI 1640 medium (Lonza Walkersville, Walkersville, MD) supplemented with fetal calf serum (Lonza Walkersville). For analysis of secreted proteins, to avoid the masking effects of high-abundance serum proteins in the culture medium, the cells were washed 3 times with RPMI 1640 medium to deplete all serum proteins, and cultured in RPMI 1640 medium without serum for 24 hours. Under these conditions, cell via...

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Immunohistochemical demonstration of cathepsin B in the macrophages of benign and malignant lymphoid tissues

Cited by 41 publications

References 22 publications

Cysteine endopeptidase activity levels in normal human tissues, colorectal adenomas and carcinomas

Cysteine endopeptidase activity levels in normal human tissues, colorectal adenomas and carcinomas

Characterization of verruciform xanthoma by in situ hybridization and immunohistochemistry

Proteomics analysis of Hodgkin lymphoma: identification of new players involved in the cross-talk between HRS cells and infiltrating lymphocytes

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