Expression of endogenous granzyme B in a subset of human primary breast carcinomas

Hu, Shi‐Xue; Wang, S.; Wang, J. P.; Mills, Gordon B.; Zhou, Yi; Xu, Hong‐Ji

doi:10.1038/sj.bjc.6601051

Cited by 39 publications

(30 citation statements)

References 30 publications

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“…For many years, granzyme B had been thought to be expressed in a limited panel of cells; however, it has recently been found in chondrocytes, 10 neutrophils, 11 and some malignant cells. 12,13 Using immunohistochemical, in Abstract Granzyme B is a unique serine protease, which plays a crucial role for target cell death. Several mechanisms of delivery of granzyme B to target cells have been recently identified.…”

Section: Granzyme B and Its Inhibitor Proteinase Inhibitormentioning

confidence: 99%

Granzyme B and natural killer (NK) cell death

Ida¹,

Utz²,

Anderson³

et al. 2005

Mod Rheumatol

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Granzyme B is a unique serine protease, which plays a crucial role for target cell death. Several mechanisms of delivery of granzyme B to target cells have been recently identified. Granzyme B directly activates Bid, a specific substrate for granzyme B, resulting in caspase activation. Granzyme B efficiently cleaves many prominent autoantigens, and the hypothesis that autoantibodies arise when cryptic determinants are revealed to the immune system has been proposed. Some autoantibodies directed against granzyme B-specific neoepitopes are present in serum from patients with autoimmune diseases. In the tissues from autoimmune diseases, granzyme B might play an important role for disease progression (i.e., rheumatoid arthritis synovium) or inhibition (i.e., regulatory T cells). We have identified a novel type of activation-induced cell death (granzyme B leakage-induced cell death). Activation-induced natural killer (NK) cell death is accompanied by the leakage of granzyme B from intracellular granules into the cytoplasm, and it triggers apoptosis by directing Bid to mitochondrial membranes. An excess of "leaked" granzyme B over its inhibitor, serpin proteinase inhibitor 9, is a major determinant of cell death. The role of granzyme B in autoimmunity and its influence on NK cell death are discussed.

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Section: Granzyme B and Its Inhibitor Proteinase Inhibitormentioning

confidence: 99%

Granzyme B and natural killer (NK) cell death

Ida¹,

Utz²,

Anderson³

et al. 2005

Mod Rheumatol

View full text Add to dashboard Cite

show abstract

“…Five microgram of total RNAs isolated from cells were treated with RNase free DNase (BD-Pharmingen), and then used to generate first-strand cDNAs using RevertAid TM first strand cDNA synthesis kit with 500 ng oligo (dT) [12][13][14][15][16][17][18] primers. PCR primers were designed with ABI PRISM Primer Express 2.0 (Applied Biosystems) and made by GenoTech Corp. (Korea).…”

Section: Rt-pcrmentioning

confidence: 99%

“…Several studies have suggested that granzyme B is produced by cells other than CTLs and NKs. Granzyme B is produced, in the absence of perforin, by the cells of the reproductive system [15], the granulose cells of human ovaries [16], primary human breast carcinomas [17], and the chondrocytes of articular cartilage [18]. The expression of granzyme B has also been detected in human dendritic cells, where it is up-regulated upon cell activation, and in migrating immature thymocytes [19][20][21].…”

Section: Introductionmentioning

confidence: 99%

Macrophages express granzyme B in the lesion areas of atherosclerosis and rheumatoid arthritis

Kim

Suk

et al. 2007

Immunology Letters

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“…Interestingly, GrB has been detected in cancer cells of primary human breast carcinomas (88,89), lung carcinomas (88), urothelial carcinomas (90) and in nasal-type NK/T-cell lymphoma (91). Recently, GrB expression was revealed by immunohistochemistry in oral squamous cell carcinoma and it seems to be localized also in cancer cells (92).…”

Section: Granzyme B Gene Organization and Regulation Of Expressionmentioning

confidence: 99%

Granzyme B-induced apoptosis in cancer cells and its regulation (Review)

Krepela¹

2010

Int J Oncol

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Abstract. The granzyme B-induced cell death has been traditionally viewed as a primary mechanism that is used by cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells to eliminate harmful target cells including allogeneic, virally infected and tumour cells. Granzyme B (GrB) is the most abundant serine protease which is stored in secretory granules of CTLs and NK cells. After recognition of the target cell, the engaged CTLs and NK cells vectorially secrete GrB along with other granule proteins including perforin into the immunological synapse. From this submicroscopic intercellular cleft GrB translocates into the cytoplasm of the target cell. Although several models have been proposed to explain the GrB delivery mechanism, conclusive understanding of this process remains still elusive. Once in the cytoplasm, GrB cleaves and activates, or inactivates, multiple protein substrates, resulting eventually into apoptotic demise of the target cell. This review is focused on the gene structure and expression of GrB, its biosynthesis and activation, delivery mechanisms into the target cell cytoplasm, direct proteolytic involvement in activation of several pro-apoptotic pathways, and on regulation of its activity in cancer cells. Moreover, emphasis is given to the GrB-mediated anticancer effects and future clinical applications of the GrB-based and tumour-targeted recombinant fusion constructs. Contents1. Introduction 2. Granzyme B gene organization and regulation of expression 3. Granzyme B biosynthesis, subcellular localization and activation 4. Granzyme B structure and substrate specificity 5. Granzyme B delivery mechanism into the target cell cytoplasm 6. Death pathways activated by granzyme B in cancer cells 7. Regulation of granzyme B activity 8. Granzyme B and anticancer therapy 9. Conclusion and the future directions of research IntroductionSusceptibility of tumour cells to apoptotic death depends on their capabilities to express the components of apoptosis pathways and to activate them in response to extrinsic or intrinsic death signals. The extrinsic death pathways are represented by the death receptor-and the cytotoxic granulemediated pathways. On the other hand, the intrinsic death mechanisms are represented by the mitochondrial, lysosomal and PIDDosome death pathways.The death receptor pathway is triggered by the binding of a death ligand, such as FasL (also known as CD95L) and TRAIL (also known as APO-2L) to a specific transmembrane death receptors, Fas (also known as APO-1/CD95) and death receptor 4 and/or 5 (DR4, DR5), respectively (1,2). After binding of the cytosolic Fas-associated death domain adaptor protein (FADD, also known as MORT1) to the liganded death receptors, the initiator procaspase-8 and/or -10 are bound to engaged FADD completing the formation of the deathinducing signalling complexes (DISCs) (1-4). Within DISCs, procaspase-8 and -10 are activated via homodimerization and the active caspase-8 and -10, arising through interdimer proteolytic processing, dissociate from DISCs into the cyt...

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Expression of endogenous granzyme B in a subset of human primary breast carcinomas

Cited by 39 publications

References 30 publications

Granzyme B and natural killer (NK) cell death

Granzyme B and natural killer (NK) cell death

Macrophages express granzyme B in the lesion areas of atherosclerosis and rheumatoid arthritis

Granzyme B-induced apoptosis in cancer cells and its regulation (Review)

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