The Emerging Role of Amino Acids of the Brain Microenvironment in the Process of Metastasis Formation
Brain metastases are the most severe clinical manifestation of aggressive tumors. Melanoma, breast, and lung cancers are the types that prefer the brain as a site of metastasis formation, even if the reasons for this phenomenon still remain to be clarified. One of the main characteristics that makes...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-06-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/13/12/2891 |
| _version_ | 1797530839732453376 |
|---|---|
| author | Francesca Cutruzzolà Amani Bouzidi Francesca Romana Liberati Sharon Spizzichino Giovanna Boumis Alberto Macone Serena Rinaldo Giorgio Giardina Alessio Paone |
| author_facet | Francesca Cutruzzolà Amani Bouzidi Francesca Romana Liberati Sharon Spizzichino Giovanna Boumis Alberto Macone Serena Rinaldo Giorgio Giardina Alessio Paone |
| author_sort | Francesca Cutruzzolà |
| collection | DOAJ |
| description | Brain metastases are the most severe clinical manifestation of aggressive tumors. Melanoma, breast, and lung cancers are the types that prefer the brain as a site of metastasis formation, even if the reasons for this phenomenon still remain to be clarified. One of the main characteristics that makes a cancer cell able to form metastases in the brain is the ability to interact with the endothelial cells of the microvasculature, cross the blood–brain barrier, and metabolically adapt to the nutrients available in the new microenvironment. In this review, we analyzed what makes the brain a suitable site for the development of metastases and how this microenvironment, through the continuous release of neurotransmitters and amino acids in the extracellular milieu, is able to support the metabolic needs of metastasizing cells. We also suggested a possible role for amino acids released by the brain through the endothelial cells of the blood–brain barrier into the bloodstream in triggering the process of extravasation/invasion of the brain parenchyma. |
| first_indexed | 2024-03-10T10:34:43Z |
| format | Article |
| id | doaj.art-f8d9302964644b968bdce93dd4f83a28 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T10:34:43Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-f8d9302964644b968bdce93dd4f83a282023-11-21T23:25:14ZengMDPI AGCancers2072-66942021-06-011312289110.3390/cancers13122891The Emerging Role of Amino Acids of the Brain Microenvironment in the Process of Metastasis FormationFrancesca Cutruzzolà0Amani Bouzidi1Francesca Romana Liberati2Sharon Spizzichino3Giovanna Boumis4Alberto Macone5Serena Rinaldo6Giorgio Giardina7Alessio Paone8Laboratory Affiliated to Istituto Pasteur Italia, Department of Biochemical Sciences A. Rossi Fanelli, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, ItalyLaboratory Affiliated to Istituto Pasteur Italia, Department of Biochemical Sciences A. Rossi Fanelli, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, ItalyLaboratory Affiliated to Istituto Pasteur Italia, Department of Biochemical Sciences A. Rossi Fanelli, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, ItalyLaboratory Affiliated to Istituto Pasteur Italia, Department of Biochemical Sciences A. Rossi Fanelli, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, ItalyLaboratory Affiliated to Istituto Pasteur Italia, Department of Biochemical Sciences A. Rossi Fanelli, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, ItalyLaboratory Affiliated to Istituto Pasteur Italia, Department of Biochemical Sciences A. Rossi Fanelli, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, ItalyLaboratory Affiliated to Istituto Pasteur Italia, Department of Biochemical Sciences A. Rossi Fanelli, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, ItalyLaboratory Affiliated to Istituto Pasteur Italia, Department of Biochemical Sciences A. Rossi Fanelli, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, ItalyLaboratory Affiliated to Istituto Pasteur Italia, Department of Biochemical Sciences A. Rossi Fanelli, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, ItalyBrain metastases are the most severe clinical manifestation of aggressive tumors. Melanoma, breast, and lung cancers are the types that prefer the brain as a site of metastasis formation, even if the reasons for this phenomenon still remain to be clarified. One of the main characteristics that makes a cancer cell able to form metastases in the brain is the ability to interact with the endothelial cells of the microvasculature, cross the blood–brain barrier, and metabolically adapt to the nutrients available in the new microenvironment. In this review, we analyzed what makes the brain a suitable site for the development of metastases and how this microenvironment, through the continuous release of neurotransmitters and amino acids in the extracellular milieu, is able to support the metabolic needs of metastasizing cells. We also suggested a possible role for amino acids released by the brain through the endothelial cells of the blood–brain barrier into the bloodstream in triggering the process of extravasation/invasion of the brain parenchyma.https://www.mdpi.com/2072-6694/13/12/2891metastasisbrain microenvironmentorganotropismneurotransmittersamino acidsmetabolism |
| spellingShingle | Francesca Cutruzzolà Amani Bouzidi Francesca Romana Liberati Sharon Spizzichino Giovanna Boumis Alberto Macone Serena Rinaldo Giorgio Giardina Alessio Paone The Emerging Role of Amino Acids of the Brain Microenvironment in the Process of Metastasis Formation Cancers metastasis brain microenvironment organotropism neurotransmitters amino acids metabolism |
| title | The Emerging Role of Amino Acids of the Brain Microenvironment in the Process of Metastasis Formation |
| title_full | The Emerging Role of Amino Acids of the Brain Microenvironment in the Process of Metastasis Formation |
| title_fullStr | The Emerging Role of Amino Acids of the Brain Microenvironment in the Process of Metastasis Formation |
| title_full_unstemmed | The Emerging Role of Amino Acids of the Brain Microenvironment in the Process of Metastasis Formation |
| title_short | The Emerging Role of Amino Acids of the Brain Microenvironment in the Process of Metastasis Formation |
| title_sort | emerging role of amino acids of the brain microenvironment in the process of metastasis formation |
| topic | metastasis brain microenvironment organotropism neurotransmitters amino acids metabolism |
| url | https://www.mdpi.com/2072-6694/13/12/2891 |
| work_keys_str_mv | AT francescacutruzzola theemergingroleofaminoacidsofthebrainmicroenvironmentintheprocessofmetastasisformation AT amanibouzidi theemergingroleofaminoacidsofthebrainmicroenvironmentintheprocessofmetastasisformation AT francescaromanaliberati theemergingroleofaminoacidsofthebrainmicroenvironmentintheprocessofmetastasisformation AT sharonspizzichino theemergingroleofaminoacidsofthebrainmicroenvironmentintheprocessofmetastasisformation AT giovannaboumis theemergingroleofaminoacidsofthebrainmicroenvironmentintheprocessofmetastasisformation AT albertomacone theemergingroleofaminoacidsofthebrainmicroenvironmentintheprocessofmetastasisformation AT serenarinaldo theemergingroleofaminoacidsofthebrainmicroenvironmentintheprocessofmetastasisformation AT giorgiogiardina theemergingroleofaminoacidsofthebrainmicroenvironmentintheprocessofmetastasisformation AT alessiopaone theemergingroleofaminoacidsofthebrainmicroenvironmentintheprocessofmetastasisformation AT francescacutruzzola emergingroleofaminoacidsofthebrainmicroenvironmentintheprocessofmetastasisformation AT amanibouzidi emergingroleofaminoacidsofthebrainmicroenvironmentintheprocessofmetastasisformation AT francescaromanaliberati emergingroleofaminoacidsofthebrainmicroenvironmentintheprocessofmetastasisformation AT sharonspizzichino emergingroleofaminoacidsofthebrainmicroenvironmentintheprocessofmetastasisformation AT giovannaboumis emergingroleofaminoacidsofthebrainmicroenvironmentintheprocessofmetastasisformation AT albertomacone emergingroleofaminoacidsofthebrainmicroenvironmentintheprocessofmetastasisformation AT serenarinaldo emergingroleofaminoacidsofthebrainmicroenvironmentintheprocessofmetastasisformation AT giorgiogiardina emergingroleofaminoacidsofthebrainmicroenvironmentintheprocessofmetastasisformation AT alessiopaone emergingroleofaminoacidsofthebrainmicroenvironmentintheprocessofmetastasisformation |