The Role of the Ectopeptidase APN/CD13 in Cancer
APN/CD13 is expressed in a variety of cells/tissues and is therefore associated with diverse physiological functions, including proliferation, differentiation, migration, angiogenesis, invasion, metastasis, vasoconstriction, and the regulation of normal and impaired immune function. Increased expres...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-02-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/11/3/724 |
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| author | Uwe Lendeckel Farzaneh Karimi Ruba Al Abdulla Carmen Wolke |
| author_facet | Uwe Lendeckel Farzaneh Karimi Ruba Al Abdulla Carmen Wolke |
| author_sort | Uwe Lendeckel |
| collection | DOAJ |
| description | APN/CD13 is expressed in a variety of cells/tissues and is therefore associated with diverse physiological functions, including proliferation, differentiation, migration, angiogenesis, invasion, metastasis, vasoconstriction, and the regulation of normal and impaired immune function. Increased expression or activity of APN/CD13 has been described for various tumors, such that APN/CD13 is in most cases associated with reduced disease-free and overall survival. The mechanisms that mediate these cellular effects of APN/CD13 have been largely determined and are described here. APN/CD13-regulated signaling pathways include integrin recycling, the regulation of small GTPase activities, cell–ECM interactions, and Erk1/2, PI3K, and Wnt signaling. APN/CD13 is a neo-angiogenesis marker that is not found on normal endothelia, but it is found on neo-angiogenetically active endothelia. Therefore, APN/CD13 represents a specific receptor for so-called “tumor-homing peptides” (NRG peptides). Peptides containing the NRG motif show high-affinity binding to APN/CD13. APN/CD13 thus represents a versatile target for the inhibition of tumor-induced angiogenesis through the tumor-selective administration of, e.g., cytotoxic substances. Furthermore, it enables the molecular imaging of tumor masses and the assessment of (neo)angiogenesis in animal models and in patients. Pharmacological inhibitors of APN/CD13 have been proven to reduce tumor growth and tumor progression in various APN/CD13-positive tumors. |
| first_indexed | 2024-03-11T06:54:17Z |
| format | Article |
| id | doaj.art-32fc74fe931c4e20835940961ccff5e8 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-11T06:54:17Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-32fc74fe931c4e20835940961ccff5e82023-11-17T09:44:42ZengMDPI AGBiomedicines2227-90592023-02-0111372410.3390/biomedicines11030724The Role of the Ectopeptidase APN/CD13 in CancerUwe Lendeckel0Farzaneh Karimi1Ruba Al Abdulla2Carmen Wolke3Institute of Medical Biochemistry and Molecular Biology, University Medicine Greifswald, University of Greifswald, D-17475 Greifswald, GermanyInstitute of Medical Biochemistry and Molecular Biology, University Medicine Greifswald, University of Greifswald, D-17475 Greifswald, GermanyInstitute of Medical Biochemistry and Molecular Biology, University Medicine Greifswald, University of Greifswald, D-17475 Greifswald, GermanyInstitute of Medical Biochemistry and Molecular Biology, University Medicine Greifswald, University of Greifswald, D-17475 Greifswald, GermanyAPN/CD13 is expressed in a variety of cells/tissues and is therefore associated with diverse physiological functions, including proliferation, differentiation, migration, angiogenesis, invasion, metastasis, vasoconstriction, and the regulation of normal and impaired immune function. Increased expression or activity of APN/CD13 has been described for various tumors, such that APN/CD13 is in most cases associated with reduced disease-free and overall survival. The mechanisms that mediate these cellular effects of APN/CD13 have been largely determined and are described here. APN/CD13-regulated signaling pathways include integrin recycling, the regulation of small GTPase activities, cell–ECM interactions, and Erk1/2, PI3K, and Wnt signaling. APN/CD13 is a neo-angiogenesis marker that is not found on normal endothelia, but it is found on neo-angiogenetically active endothelia. Therefore, APN/CD13 represents a specific receptor for so-called “tumor-homing peptides” (NRG peptides). Peptides containing the NRG motif show high-affinity binding to APN/CD13. APN/CD13 thus represents a versatile target for the inhibition of tumor-induced angiogenesis through the tumor-selective administration of, e.g., cytotoxic substances. Furthermore, it enables the molecular imaging of tumor masses and the assessment of (neo)angiogenesis in animal models and in patients. Pharmacological inhibitors of APN/CD13 have been proven to reduce tumor growth and tumor progression in various APN/CD13-positive tumors.https://www.mdpi.com/2227-9059/11/3/724aminopeptidase NangiogenesisANPEPcancercancer stem cellsdrug resistance |
| spellingShingle | Uwe Lendeckel Farzaneh Karimi Ruba Al Abdulla Carmen Wolke The Role of the Ectopeptidase APN/CD13 in Cancer Biomedicines aminopeptidase N angiogenesis ANPEP cancer cancer stem cells drug resistance |
| title | The Role of the Ectopeptidase APN/CD13 in Cancer |
| title_full | The Role of the Ectopeptidase APN/CD13 in Cancer |
| title_fullStr | The Role of the Ectopeptidase APN/CD13 in Cancer |
| title_full_unstemmed | The Role of the Ectopeptidase APN/CD13 in Cancer |
| title_short | The Role of the Ectopeptidase APN/CD13 in Cancer |
| title_sort | role of the ectopeptidase apn cd13 in cancer |
| topic | aminopeptidase N angiogenesis ANPEP cancer cancer stem cells drug resistance |
| url | https://www.mdpi.com/2227-9059/11/3/724 |
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