Hypoxic Effects on Matrix Metalloproteinases’ Expression in the Tumor Microenvironment and Therapeutic Perspectives
The tumor microenvironment (TME) is characterized by an acidic pH and low oxygen concentrations. Hypoxia induces neoplastic cell evasion of the immune surveillance, rapid DNA repair, metabolic reprogramming, and metastasis, mainly as a response to the hypoxic inducible factors (HIFs). Likewise, canc...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/23/16887 |
| _version_ | 1797400025317244928 |
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| author | Georgina Gonzalez-Avila Bettina Sommer Edgar Flores-Soto Arnoldo Aquino-Galvez |
| author_facet | Georgina Gonzalez-Avila Bettina Sommer Edgar Flores-Soto Arnoldo Aquino-Galvez |
| author_sort | Georgina Gonzalez-Avila |
| collection | DOAJ |
| description | The tumor microenvironment (TME) is characterized by an acidic pH and low oxygen concentrations. Hypoxia induces neoplastic cell evasion of the immune surveillance, rapid DNA repair, metabolic reprogramming, and metastasis, mainly as a response to the hypoxic inducible factors (HIFs). Likewise, cancer cells increase matrix metalloproteinases’ (MMPs) expression in response to TME conditions, allowing them to migrate from the primary tumor to different tissues. Since HIFs and MMPs are augmented in the hypoxic TME, it is easy to consider that HIFs participate directly in their expression regulation. However, not all MMPs have a hypoxia response element (HRE)-HIF binding site. Moreover, different transcription factors and signaling pathways activated in hypoxia conditions through HIFs or in a HIF-independent manner participate in MMPs’ transcription. The present review focuses on MMPs’ expression in normal and hypoxic conditions, considering HIFs and a HIF-independent transcription control. In addition, since the hypoxic TME causes resistance to anticancer conventional therapy, treatment approaches using MMPs as a target alone, or in combination with other therapies, are also discussed. |
| first_indexed | 2024-03-09T01:49:36Z |
| format | Article |
| id | doaj.art-198d975ed1da43b78c12f1b904325dd2 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T01:49:36Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-198d975ed1da43b78c12f1b904325dd22023-12-08T15:17:30ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-11-0124231688710.3390/ijms242316887Hypoxic Effects on Matrix Metalloproteinases’ Expression in the Tumor Microenvironment and Therapeutic PerspectivesGeorgina Gonzalez-Avila0Bettina Sommer1Edgar Flores-Soto2Arnoldo Aquino-Galvez3Laboratorio de Oncología Biomédica, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Calzada de Tlalpan 4502, Col. Sección XVI, Tlalpan, Ciudad de México 14080, MexicoDepartamento de Investigación en Hiperreactividad Bronquial, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Calzada de Tlalpan 4502, Col. Sección XVI, Tlalpan, Ciudad de México 14080, MexicoDepartamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México, Coyoacán, Ciudad de México 04510, MexicoLaboratorio de Biología Molecular, Departamento de Fibrosis Pulmonar, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Calzada de Tlalpan 4502, Col. Sección XVI, Tlalpan, Ciudad de México 14080, MexicoThe tumor microenvironment (TME) is characterized by an acidic pH and low oxygen concentrations. Hypoxia induces neoplastic cell evasion of the immune surveillance, rapid DNA repair, metabolic reprogramming, and metastasis, mainly as a response to the hypoxic inducible factors (HIFs). Likewise, cancer cells increase matrix metalloproteinases’ (MMPs) expression in response to TME conditions, allowing them to migrate from the primary tumor to different tissues. Since HIFs and MMPs are augmented in the hypoxic TME, it is easy to consider that HIFs participate directly in their expression regulation. However, not all MMPs have a hypoxia response element (HRE)-HIF binding site. Moreover, different transcription factors and signaling pathways activated in hypoxia conditions through HIFs or in a HIF-independent manner participate in MMPs’ transcription. The present review focuses on MMPs’ expression in normal and hypoxic conditions, considering HIFs and a HIF-independent transcription control. In addition, since the hypoxic TME causes resistance to anticancer conventional therapy, treatment approaches using MMPs as a target alone, or in combination with other therapies, are also discussed.https://www.mdpi.com/1422-0067/24/23/16887cancer treatmentHIFshypoxiamatrix metalloproteinasesnanotechnologytumor microenvironment |
| spellingShingle | Georgina Gonzalez-Avila Bettina Sommer Edgar Flores-Soto Arnoldo Aquino-Galvez Hypoxic Effects on Matrix Metalloproteinases’ Expression in the Tumor Microenvironment and Therapeutic Perspectives International Journal of Molecular Sciences cancer treatment HIFs hypoxia matrix metalloproteinases nanotechnology tumor microenvironment |
| title | Hypoxic Effects on Matrix Metalloproteinases’ Expression in the Tumor Microenvironment and Therapeutic Perspectives |
| title_full | Hypoxic Effects on Matrix Metalloproteinases’ Expression in the Tumor Microenvironment and Therapeutic Perspectives |
| title_fullStr | Hypoxic Effects on Matrix Metalloproteinases’ Expression in the Tumor Microenvironment and Therapeutic Perspectives |
| title_full_unstemmed | Hypoxic Effects on Matrix Metalloproteinases’ Expression in the Tumor Microenvironment and Therapeutic Perspectives |
| title_short | Hypoxic Effects on Matrix Metalloproteinases’ Expression in the Tumor Microenvironment and Therapeutic Perspectives |
| title_sort | hypoxic effects on matrix metalloproteinases expression in the tumor microenvironment and therapeutic perspectives |
| topic | cancer treatment HIFs hypoxia matrix metalloproteinases nanotechnology tumor microenvironment |
| url | https://www.mdpi.com/1422-0067/24/23/16887 |
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