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Cancer stem cell mobilization and therapeutic targeting of the 5T4 oncofetal antigen

Cancer stem cells (CSCs) can act as the cellular drivers of tumors harnessing stem cell properties that contribute to tumorigenesis either as founder elements or by the gain of stem cell traits by the malignant cells. Thus, CSCs can self-renew and generate the cellular heterogeneity of tumors includ...

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Autores principales: Harrop, Richard, O’Neill, Eric, Stern, Peter L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6348545/
https://www.ncbi.nlm.nih.gov/pubmed/30719508
http://dx.doi.org/10.1177/2515135518821623
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author Harrop, Richard
O’Neill, Eric
Stern, Peter L.
author_facet Harrop, Richard
O’Neill, Eric
Stern, Peter L.
author_sort Harrop, Richard
collection PubMed
description Cancer stem cells (CSCs) can act as the cellular drivers of tumors harnessing stem cell properties that contribute to tumorigenesis either as founder elements or by the gain of stem cell traits by the malignant cells. Thus, CSCs can self-renew and generate the cellular heterogeneity of tumors including a hierarchical organization similar to the normal tissue. While the principle tumor growth contribution is often from the non-CSC components, it is the ability of small numbers of CSCs to avoid the effects of therapeutic strategies that can contribute to recurrence after treatment. However, identifying and characterizing CSCs for therapeutic targeting is made more challenging by their cellular potency being influenced by a particular tissue niche or by the capacity of more committed cells to regain stem cell functions. This review discusses the properties of CSCs including the limitations of the available cell surface markers, the assays that document tumor initiation and clonogenicity, the roles of epithelial mesenchymal transition and molecular pathways such as Notch, Wnt, Hippo and Hedgehog. The ability to target and eliminate CSCs is thought to be critical in the search for curative cancer treatments. The oncofetal tumor-associated antigen 5T4 (TBGP) has been linked with CSC properties in several different malignancies. 5T4 has functional attributes that are relevant to the spread of tumors including through EMT, CXCR4/CXCL12, Wnt, and Hippo pathways which may all contribute through the mobilization of CSCs. There are several different immunotherapies targeting 5T4 in development including antibody–drug conjugates, antibody-targeted bacterial super-antigens, a Modified Vaccinia Ankara-basedvaccine and 5T4-directed chimeric antigen receptor T-cells. These immune therapies would have the advantage of targeting both the bulk tumor as well as mobilized CSC populations.
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spelling pubmed-63485452019-02-04 Cancer stem cell mobilization and therapeutic targeting of the 5T4 oncofetal antigen Harrop, Richard O’Neill, Eric Stern, Peter L. Ther Adv Vaccines Immunother Review Cancer stem cells (CSCs) can act as the cellular drivers of tumors harnessing stem cell properties that contribute to tumorigenesis either as founder elements or by the gain of stem cell traits by the malignant cells. Thus, CSCs can self-renew and generate the cellular heterogeneity of tumors including a hierarchical organization similar to the normal tissue. While the principle tumor growth contribution is often from the non-CSC components, it is the ability of small numbers of CSCs to avoid the effects of therapeutic strategies that can contribute to recurrence after treatment. However, identifying and characterizing CSCs for therapeutic targeting is made more challenging by their cellular potency being influenced by a particular tissue niche or by the capacity of more committed cells to regain stem cell functions. This review discusses the properties of CSCs including the limitations of the available cell surface markers, the assays that document tumor initiation and clonogenicity, the roles of epithelial mesenchymal transition and molecular pathways such as Notch, Wnt, Hippo and Hedgehog. The ability to target and eliminate CSCs is thought to be critical in the search for curative cancer treatments. The oncofetal tumor-associated antigen 5T4 (TBGP) has been linked with CSC properties in several different malignancies. 5T4 has functional attributes that are relevant to the spread of tumors including through EMT, CXCR4/CXCL12, Wnt, and Hippo pathways which may all contribute through the mobilization of CSCs. There are several different immunotherapies targeting 5T4 in development including antibody–drug conjugates, antibody-targeted bacterial super-antigens, a Modified Vaccinia Ankara-basedvaccine and 5T4-directed chimeric antigen receptor T-cells. These immune therapies would have the advantage of targeting both the bulk tumor as well as mobilized CSC populations. SAGE Publications 2019-01-25 /pmc/articles/PMC6348545/ /pubmed/30719508 http://dx.doi.org/10.1177/2515135518821623 Text en © The Author(s), 2019 http://www.creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Review
Harrop, Richard
O’Neill, Eric
Stern, Peter L.
Cancer stem cell mobilization and therapeutic targeting of the 5T4 oncofetal antigen
title Cancer stem cell mobilization and therapeutic targeting of the 5T4 oncofetal antigen
title_full Cancer stem cell mobilization and therapeutic targeting of the 5T4 oncofetal antigen
title_fullStr Cancer stem cell mobilization and therapeutic targeting of the 5T4 oncofetal antigen
title_full_unstemmed Cancer stem cell mobilization and therapeutic targeting of the 5T4 oncofetal antigen
title_short Cancer stem cell mobilization and therapeutic targeting of the 5T4 oncofetal antigen
title_sort cancer stem cell mobilization and therapeutic targeting of the 5t4 oncofetal antigen
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6348545/
https://www.ncbi.nlm.nih.gov/pubmed/30719508
http://dx.doi.org/10.1177/2515135518821623
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