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Thrombin Cleavage of Osteopontin and the Host Anti-Tumor Immune Response

SIMPLE SUMMARY: Osteopontin (OPN) is a protein produced by immune cells, as well as many other cell types including tumor cells, that is highly modified with sugars and phosphates. OPN binds to receptors present on many cell types including cancer and immune cells and causes those cells to change pr...

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Autores principales: Leung, Lawrence L., Myles, Timothy, Morser, John
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10340489/
https://www.ncbi.nlm.nih.gov/pubmed/37444590
http://dx.doi.org/10.3390/cancers15133480
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author Leung, Lawrence L.
Myles, Timothy
Morser, John
author_facet Leung, Lawrence L.
Myles, Timothy
Morser, John
author_sort Leung, Lawrence L.
collection PubMed
description SIMPLE SUMMARY: Osteopontin (OPN) is a protein produced by immune cells, as well as many other cell types including tumor cells, that is highly modified with sugars and phosphates. OPN binds to receptors present on many cell types including cancer and immune cells and causes those cells to change properties. OPN is increased in the blood of cancer patients. OPN can be cut by thrombin, the major enzyme responsible for blood clotting, into two fragments that have different properties from intact OPN. These fragments suppress the host’s immune response to cancer, allowing the cancer to grow faster and to metastasize. ABSTRACT: Osteopontin (OPN) is a multi-functional protein that is involved in various cellular processes such as cell adhesion, migration, and signaling. There is a single conserved thrombin cleavage site in OPN that, when cleaved, yields two fragments with different properties from full-length OPN. In cancer, OPN has tumor-promoting activity and plays a role in tumor growth and metastasis. High levels of OPN expression in cancer cells and tumor tissue are found in various types of cancer, including breast, lung, prostate, ovarian, colorectal, and pancreatic cancer, and are associated with poor prognosis and decreased survival rates. OPN promotes tumor progression and invasion by stimulating cell proliferation and angiogenesis and also facilitates the metastasis of cancer cells to other parts of the body by promoting cell adhesion and migration. Furthermore, OPN contributes to immune evasion by inhibiting the activity of immune cells. Thrombin cleavage of OPN initiates OPN’s tumor-promoting activity, and thrombin cleavage fragments of OPN down-regulate the host immune anti-tumor response.
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spelling pubmed-103404892023-07-14 Thrombin Cleavage of Osteopontin and the Host Anti-Tumor Immune Response Leung, Lawrence L. Myles, Timothy Morser, John Cancers (Basel) Review SIMPLE SUMMARY: Osteopontin (OPN) is a protein produced by immune cells, as well as many other cell types including tumor cells, that is highly modified with sugars and phosphates. OPN binds to receptors present on many cell types including cancer and immune cells and causes those cells to change properties. OPN is increased in the blood of cancer patients. OPN can be cut by thrombin, the major enzyme responsible for blood clotting, into two fragments that have different properties from intact OPN. These fragments suppress the host’s immune response to cancer, allowing the cancer to grow faster and to metastasize. ABSTRACT: Osteopontin (OPN) is a multi-functional protein that is involved in various cellular processes such as cell adhesion, migration, and signaling. There is a single conserved thrombin cleavage site in OPN that, when cleaved, yields two fragments with different properties from full-length OPN. In cancer, OPN has tumor-promoting activity and plays a role in tumor growth and metastasis. High levels of OPN expression in cancer cells and tumor tissue are found in various types of cancer, including breast, lung, prostate, ovarian, colorectal, and pancreatic cancer, and are associated with poor prognosis and decreased survival rates. OPN promotes tumor progression and invasion by stimulating cell proliferation and angiogenesis and also facilitates the metastasis of cancer cells to other parts of the body by promoting cell adhesion and migration. Furthermore, OPN contributes to immune evasion by inhibiting the activity of immune cells. Thrombin cleavage of OPN initiates OPN’s tumor-promoting activity, and thrombin cleavage fragments of OPN down-regulate the host immune anti-tumor response. MDPI 2023-07-03 /pmc/articles/PMC10340489/ /pubmed/37444590 http://dx.doi.org/10.3390/cancers15133480 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Leung, Lawrence L.
Myles, Timothy
Morser, John
Thrombin Cleavage of Osteopontin and the Host Anti-Tumor Immune Response
title Thrombin Cleavage of Osteopontin and the Host Anti-Tumor Immune Response
title_full Thrombin Cleavage of Osteopontin and the Host Anti-Tumor Immune Response
title_fullStr Thrombin Cleavage of Osteopontin and the Host Anti-Tumor Immune Response
title_full_unstemmed Thrombin Cleavage of Osteopontin and the Host Anti-Tumor Immune Response
title_short Thrombin Cleavage of Osteopontin and the Host Anti-Tumor Immune Response
title_sort thrombin cleavage of osteopontin and the host anti-tumor immune response
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10340489/
https://www.ncbi.nlm.nih.gov/pubmed/37444590
http://dx.doi.org/10.3390/cancers15133480
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