The promising therapeutic effects of metformin on metabolic reprogramming of cancer-associated fibroblasts in solid tumors
Abstract Tumor-infiltrated lymphocytes are exposed to many toxic metabolites and molecules in the tumor microenvironment (TME) that suppress their anti-tumor activity. Toxic metabolites, such as lactate and ketone bodies, are produced mainly by catabolic cancer-associated fibroblasts (CAFs) to feed...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-07-01
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| Series: | Cellular & Molecular Biology Letters |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s11658-022-00356-2 |
| _version_ | 1811287440570187776 |
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| author | Samaneh Mostafavi Hamidreza Zalpoor Zuhair Mohammad Hassan |
| author_facet | Samaneh Mostafavi Hamidreza Zalpoor Zuhair Mohammad Hassan |
| author_sort | Samaneh Mostafavi |
| collection | DOAJ |
| description | Abstract Tumor-infiltrated lymphocytes are exposed to many toxic metabolites and molecules in the tumor microenvironment (TME) that suppress their anti-tumor activity. Toxic metabolites, such as lactate and ketone bodies, are produced mainly by catabolic cancer-associated fibroblasts (CAFs) to feed anabolic cancer cells. These catabolic and anabolic cells make a metabolic compartment through which high-energy metabolites like lactate can be transferred via the monocarboxylate transporter channel 4. Moreover, a decrease in molecules, including caveolin-1, has been reported to cause deep metabolic changes in normal fibroblasts toward myofibroblast differentiation. In this context, metformin is a promising drug in cancer therapy due to its effect on oncogenic signal transduction pathways, leading to the inhibition of tumor proliferation and downregulation of key oncometabolites like lactate and succinate. The cross-feeding and metabolic coupling of CAFs and tumor cells are also affected by metformin. Therefore, the importance of metabolic reprogramming of stromal cells and also the pivotal effects of metformin on TME and oncometabolites signaling pathways have been reviewed in this study. |
| first_indexed | 2024-04-13T03:18:25Z |
| format | Article |
| id | doaj.art-5f4748b69d5b4c368911f4393c7fd185 |
| institution | Directory Open Access Journal |
| issn | 1425-8153 1689-1392 |
| language | English |
| last_indexed | 2024-04-13T03:18:25Z |
| publishDate | 2022-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Cellular & Molecular Biology Letters |
| spelling | doaj.art-5f4748b69d5b4c368911f4393c7fd1852022-12-22T03:04:50ZengBMCCellular & Molecular Biology Letters1425-81531689-13922022-07-0127112410.1186/s11658-022-00356-2The promising therapeutic effects of metformin on metabolic reprogramming of cancer-associated fibroblasts in solid tumorsSamaneh Mostafavi0Hamidreza Zalpoor1Zuhair Mohammad Hassan2Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares UniversityShiraz Neuroscience Research Center, Shiraz University of Medical SciencesDepartment of Immunology, Faculty of Medical Sciences, Tarbiat Modares UniversityAbstract Tumor-infiltrated lymphocytes are exposed to many toxic metabolites and molecules in the tumor microenvironment (TME) that suppress their anti-tumor activity. Toxic metabolites, such as lactate and ketone bodies, are produced mainly by catabolic cancer-associated fibroblasts (CAFs) to feed anabolic cancer cells. These catabolic and anabolic cells make a metabolic compartment through which high-energy metabolites like lactate can be transferred via the monocarboxylate transporter channel 4. Moreover, a decrease in molecules, including caveolin-1, has been reported to cause deep metabolic changes in normal fibroblasts toward myofibroblast differentiation. In this context, metformin is a promising drug in cancer therapy due to its effect on oncogenic signal transduction pathways, leading to the inhibition of tumor proliferation and downregulation of key oncometabolites like lactate and succinate. The cross-feeding and metabolic coupling of CAFs and tumor cells are also affected by metformin. Therefore, the importance of metabolic reprogramming of stromal cells and also the pivotal effects of metformin on TME and oncometabolites signaling pathways have been reviewed in this study.https://doi.org/10.1186/s11658-022-00356-2Tumor microenvironmentMyofibroblastsCancer-associated fibroblastsMetforminLactic acidStromal cells |
| spellingShingle | Samaneh Mostafavi Hamidreza Zalpoor Zuhair Mohammad Hassan The promising therapeutic effects of metformin on metabolic reprogramming of cancer-associated fibroblasts in solid tumors Cellular & Molecular Biology Letters Tumor microenvironment Myofibroblasts Cancer-associated fibroblasts Metformin Lactic acid Stromal cells |
| title | The promising therapeutic effects of metformin on metabolic reprogramming of cancer-associated fibroblasts in solid tumors |
| title_full | The promising therapeutic effects of metformin on metabolic reprogramming of cancer-associated fibroblasts in solid tumors |
| title_fullStr | The promising therapeutic effects of metformin on metabolic reprogramming of cancer-associated fibroblasts in solid tumors |
| title_full_unstemmed | The promising therapeutic effects of metformin on metabolic reprogramming of cancer-associated fibroblasts in solid tumors |
| title_short | The promising therapeutic effects of metformin on metabolic reprogramming of cancer-associated fibroblasts in solid tumors |
| title_sort | promising therapeutic effects of metformin on metabolic reprogramming of cancer associated fibroblasts in solid tumors |
| topic | Tumor microenvironment Myofibroblasts Cancer-associated fibroblasts Metformin Lactic acid Stromal cells |
| url | https://doi.org/10.1186/s11658-022-00356-2 |
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