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Role of the inflammatory protein serine protease inhibitor Kazal in preventing cytolytic granule granzyme A-mediated apoptosis
Journal article   Open access   Peer reviewed

Role of the inflammatory protein serine protease inhibitor Kazal in preventing cytolytic granule granzyme A-mediated apoptosis

Felix Lu, Jason Lamontagne, Angela Sun, Mark Pinkerton, Timothy Block and Xuanyong Lu
Immunology, v 134(4), pp 398-408
Dec 2011
DOI: https://doi.org/10.1111/j.1365-2567.2011.03498.x
PMID: 22043941
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1111/j.1365-2567.2011.03498.xView
Published, Version of Record (VoR)Open Access (License Unspecified),  Open

Abstract

Antibodies, Monoclonal - immunology Apoptosis - immunology Cell Line Granzymes - immunology Granzymes - metabolism Humans Immunologic Surveillance Immunoprecipitation Immunotherapy Killer Cells, Natural - immunology Killer Cells, Natural - pathology Neoplasms - immunology Neoplasms - therapy T-Lymphocytes, Cytotoxic - immunology T-Lymphocytes, Cytotoxic - pathology Trypsin Inhibitor, Kazal Pancreatic - immunology Trypsin Inhibitor, Kazal Pancreatic - metabolism Tumor Escape - immunology
Serine protease inhibitor Kazal (SPIK) is an inflammatory protein whose levels are elevated in numerous cancers. However, the role of this protein in cancer development is unknown. We have recently found that SPIK suppresses serine protease-dependent cell apoptosis. Here, we report that anti-SPIK antibodies can co-immmunoprecipitate serine protease granzyme A (GzmA), a cytolytic granule secreted by cytotoxic T lymphocytes and natural killer cells during immune surveillance, and that SPIK suppresses GzmA-induced cell apoptosis. Deletion studies show that the C3-C4 region of SPIK is critical for this suppression. These studies suggest that over-expression of SPIK may prevent GzmA-mediated immune-killing, thereby establishing the tolerance of cancer cells to the body's immune surveillance system. Suppression of over-expressed SPIK can restore the susceptibility of these cells to apoptotic death triggered by GzmA. This finding implies that it is possible to overcome tolerance of cancer cells to the body's immune surveillance system and restore the GzmA-mediated immune-killing by suppressing the over-expression of SPIK.

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Collaboration types
Domestic collaboration
Web of Science research areas
Immunology
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