The Tumor Microenvironment in Tumorigenesis and Therapy Resistance Revisited
Tumorigenesis is a complex and dynamic process involving cell-cell and cell-extracellular matrix (ECM) interactions that allow tumor cell growth, drug resistance and metastasis. This review provides an updated summary of the role played by the tumor microenvironment (TME) components and hypoxia in t...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-01-01
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| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/15/2/376 |
| _version_ | 1797444902310641664 |
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| author | Kevin Dzobo Dimakatso A. Senthebane Collet Dandara |
| author_facet | Kevin Dzobo Dimakatso A. Senthebane Collet Dandara |
| author_sort | Kevin Dzobo |
| collection | DOAJ |
| description | Tumorigenesis is a complex and dynamic process involving cell-cell and cell-extracellular matrix (ECM) interactions that allow tumor cell growth, drug resistance and metastasis. This review provides an updated summary of the role played by the tumor microenvironment (TME) components and hypoxia in tumorigenesis, and highlight various ways through which tumor cells reprogram normal cells into phenotypes that are pro-tumorigenic, including cancer associated- fibroblasts, -macrophages and -endothelial cells. Tumor cells secrete numerous factors leading to the transformation of a previously anti-tumorigenic environment into a pro-tumorigenic environment. Once formed, solid tumors continue to interact with various stromal cells, including local and infiltrating fibroblasts, macrophages, mesenchymal stem cells, endothelial cells, pericytes, and secreted factors and the ECM within the tumor microenvironment (TME). The TME is key to tumorigenesis, drug response and treatment outcome. Importantly, stromal cells and secreted factors can initially be anti-tumorigenic, but over time promote tumorigenesis and induce therapy resistance. To counter hypoxia, increased angiogenesis leads to the formation of new vascular networks in order to actively promote and sustain tumor growth via the supply of oxygen and nutrients, whilst removing metabolic waste. Angiogenic vascular network formation aid in tumor cell metastatic dissemination. Successful tumor treatment and novel drug development require the identification and therapeutic targeting of pro-tumorigenic components of the TME including cancer-associated- fibroblasts (CAFs) and -macrophages (CAMs), hypoxia, blocking ECM-receptor interactions, in addition to the targeting of tumor cells. The reprogramming of stromal cells and the immune response to be anti-tumorigenic is key to therapeutic success. Lastly, this review highlights potential TME- and hypoxia-centered therapies under investigation. |
| first_indexed | 2024-03-09T13:18:10Z |
| format | Article |
| id | doaj.art-211441f7c0864325a7ef103a63754013 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T13:18:10Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-211441f7c0864325a7ef103a637540132023-11-30T21:33:00ZengMDPI AGCancers2072-66942023-01-0115237610.3390/cancers15020376The Tumor Microenvironment in Tumorigenesis and Therapy Resistance RevisitedKevin Dzobo0Dimakatso A. Senthebane1Collet Dandara2Wound and Keloid Scarring Research Unit, Hair and Skin Research Laboratory, Division of Dermatology, Department of Medicine, The South African Medical Research Council, Groote Schuur Hospital, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, Cape Town 7925, South AfricaDivision of Medical Biochemistry and Institute of Infectious Disease and Molecular Medicine, Department of Integrative Biomedical Sciences, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, Cape Town 7925, South AfricaDivision of Human Genetics, Department of Pathology, Faculty of Health Sciences, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Anzio Road, Observatory, Cape Town 7925, South AfricaTumorigenesis is a complex and dynamic process involving cell-cell and cell-extracellular matrix (ECM) interactions that allow tumor cell growth, drug resistance and metastasis. This review provides an updated summary of the role played by the tumor microenvironment (TME) components and hypoxia in tumorigenesis, and highlight various ways through which tumor cells reprogram normal cells into phenotypes that are pro-tumorigenic, including cancer associated- fibroblasts, -macrophages and -endothelial cells. Tumor cells secrete numerous factors leading to the transformation of a previously anti-tumorigenic environment into a pro-tumorigenic environment. Once formed, solid tumors continue to interact with various stromal cells, including local and infiltrating fibroblasts, macrophages, mesenchymal stem cells, endothelial cells, pericytes, and secreted factors and the ECM within the tumor microenvironment (TME). The TME is key to tumorigenesis, drug response and treatment outcome. Importantly, stromal cells and secreted factors can initially be anti-tumorigenic, but over time promote tumorigenesis and induce therapy resistance. To counter hypoxia, increased angiogenesis leads to the formation of new vascular networks in order to actively promote and sustain tumor growth via the supply of oxygen and nutrients, whilst removing metabolic waste. Angiogenic vascular network formation aid in tumor cell metastatic dissemination. Successful tumor treatment and novel drug development require the identification and therapeutic targeting of pro-tumorigenic components of the TME including cancer-associated- fibroblasts (CAFs) and -macrophages (CAMs), hypoxia, blocking ECM-receptor interactions, in addition to the targeting of tumor cells. The reprogramming of stromal cells and the immune response to be anti-tumorigenic is key to therapeutic success. Lastly, this review highlights potential TME- and hypoxia-centered therapies under investigation.https://www.mdpi.com/2072-6694/15/2/376tumor microenvironmentstromal cellsimmune cellsECMcancer hallmarkshypoxia |
| spellingShingle | Kevin Dzobo Dimakatso A. Senthebane Collet Dandara The Tumor Microenvironment in Tumorigenesis and Therapy Resistance Revisited Cancers tumor microenvironment stromal cells immune cells ECM cancer hallmarks hypoxia |
| title | The Tumor Microenvironment in Tumorigenesis and Therapy Resistance Revisited |
| title_full | The Tumor Microenvironment in Tumorigenesis and Therapy Resistance Revisited |
| title_fullStr | The Tumor Microenvironment in Tumorigenesis and Therapy Resistance Revisited |
| title_full_unstemmed | The Tumor Microenvironment in Tumorigenesis and Therapy Resistance Revisited |
| title_short | The Tumor Microenvironment in Tumorigenesis and Therapy Resistance Revisited |
| title_sort | tumor microenvironment in tumorigenesis and therapy resistance revisited |
| topic | tumor microenvironment stromal cells immune cells ECM cancer hallmarks hypoxia |
| url | https://www.mdpi.com/2072-6694/15/2/376 |
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