Insights into the Molecular Mechanisms Mediating Extravasation in Brain Metastasis of Breast Cancer, Melanoma, and Lung Cancer
Brain metastasis is an incurable end-stage of systemic cancer associated with poor prognosis, and its incidence is increasing. Brain metastasis occurs through a multi-step cascade where cancer cells spread from the primary tumor site to the brain. The extravasation of tumor cells through the blood–b...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-04-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/15/8/2258 |
| _version_ | 1797606051230515200 |
|---|---|
| author | Rama Alsabbagh Munazza Ahmed Mohammad A. Y. Alqudah Rifat Hamoudi Rania Harati |
| author_facet | Rama Alsabbagh Munazza Ahmed Mohammad A. Y. Alqudah Rifat Hamoudi Rania Harati |
| author_sort | Rama Alsabbagh |
| collection | DOAJ |
| description | Brain metastasis is an incurable end-stage of systemic cancer associated with poor prognosis, and its incidence is increasing. Brain metastasis occurs through a multi-step cascade where cancer cells spread from the primary tumor site to the brain. The extravasation of tumor cells through the blood–brain barrier (BBB) is a critical step in brain metastasis. During extravasation, circulating cancer cells roll along the brain endothelium (BE), adhere to it, then induce alterations in the endothelial barrier to transmigrate through the BBB and enter the brain. Rolling and adhesion are generally mediated by selectins and adhesion molecules induced by inflammatory mediators, while alterations in the endothelial barrier are mediated by proteolytic enzymes, including matrix metalloproteinase, and the transmigration step mediated by factors, including chemokines. However, the molecular mechanisms mediating extravasation are not yet fully understood. A better understanding of these mechanisms is essential as it may serve as the basis for the development of therapeutic strategies for the prevention or treatment of brain metastases. In this review, we summarize the molecular events that occur during the extravasation of cancer cells through the blood–brain barrier in three types of cancer most likely to develop brain metastasis: breast cancer, melanoma, and lung cancer. Common molecular mechanisms driving extravasation in these different tumors are discussed. |
| first_indexed | 2024-03-11T05:09:53Z |
| format | Article |
| id | doaj.art-3925af91897443d98a356a6088457e0a |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-11T05:09:53Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-3925af91897443d98a356a6088457e0a2023-11-17T18:38:31ZengMDPI AGCancers2072-66942023-04-01158225810.3390/cancers15082258Insights into the Molecular Mechanisms Mediating Extravasation in Brain Metastasis of Breast Cancer, Melanoma, and Lung CancerRama Alsabbagh0Munazza Ahmed1Mohammad A. Y. Alqudah2Rifat Hamoudi3Rania Harati4Department of Pharmacy Practice and Pharmacotherapeutics, College of Pharmacy, University of Sharjah, Sharjah 27272, United Arab EmiratesDepartment of Pharmacy Practice and Pharmacotherapeutics, College of Pharmacy, University of Sharjah, Sharjah 27272, United Arab EmiratesDepartment of Pharmacy Practice and Pharmacotherapeutics, College of Pharmacy, University of Sharjah, Sharjah 27272, United Arab EmiratesClinical Sciences Department, College of Medicine, University of Sharjah, Sharjah 27272, United Arab EmiratesDepartment of Pharmacy Practice and Pharmacotherapeutics, College of Pharmacy, University of Sharjah, Sharjah 27272, United Arab EmiratesBrain metastasis is an incurable end-stage of systemic cancer associated with poor prognosis, and its incidence is increasing. Brain metastasis occurs through a multi-step cascade where cancer cells spread from the primary tumor site to the brain. The extravasation of tumor cells through the blood–brain barrier (BBB) is a critical step in brain metastasis. During extravasation, circulating cancer cells roll along the brain endothelium (BE), adhere to it, then induce alterations in the endothelial barrier to transmigrate through the BBB and enter the brain. Rolling and adhesion are generally mediated by selectins and adhesion molecules induced by inflammatory mediators, while alterations in the endothelial barrier are mediated by proteolytic enzymes, including matrix metalloproteinase, and the transmigration step mediated by factors, including chemokines. However, the molecular mechanisms mediating extravasation are not yet fully understood. A better understanding of these mechanisms is essential as it may serve as the basis for the development of therapeutic strategies for the prevention or treatment of brain metastases. In this review, we summarize the molecular events that occur during the extravasation of cancer cells through the blood–brain barrier in three types of cancer most likely to develop brain metastasis: breast cancer, melanoma, and lung cancer. Common molecular mechanisms driving extravasation in these different tumors are discussed.https://www.mdpi.com/2072-6694/15/8/2258brain metastasismolecular mechanismslung cancerbreast cancermelanoma |
| spellingShingle | Rama Alsabbagh Munazza Ahmed Mohammad A. Y. Alqudah Rifat Hamoudi Rania Harati Insights into the Molecular Mechanisms Mediating Extravasation in Brain Metastasis of Breast Cancer, Melanoma, and Lung Cancer Cancers brain metastasis molecular mechanisms lung cancer breast cancer melanoma |
| title | Insights into the Molecular Mechanisms Mediating Extravasation in Brain Metastasis of Breast Cancer, Melanoma, and Lung Cancer |
| title_full | Insights into the Molecular Mechanisms Mediating Extravasation in Brain Metastasis of Breast Cancer, Melanoma, and Lung Cancer |
| title_fullStr | Insights into the Molecular Mechanisms Mediating Extravasation in Brain Metastasis of Breast Cancer, Melanoma, and Lung Cancer |
| title_full_unstemmed | Insights into the Molecular Mechanisms Mediating Extravasation in Brain Metastasis of Breast Cancer, Melanoma, and Lung Cancer |
| title_short | Insights into the Molecular Mechanisms Mediating Extravasation in Brain Metastasis of Breast Cancer, Melanoma, and Lung Cancer |
| title_sort | insights into the molecular mechanisms mediating extravasation in brain metastasis of breast cancer melanoma and lung cancer |
| topic | brain metastasis molecular mechanisms lung cancer breast cancer melanoma |
| url | https://www.mdpi.com/2072-6694/15/8/2258 |
| work_keys_str_mv | AT ramaalsabbagh insightsintothemolecularmechanismsmediatingextravasationinbrainmetastasisofbreastcancermelanomaandlungcancer AT munazzaahmed insightsintothemolecularmechanismsmediatingextravasationinbrainmetastasisofbreastcancermelanomaandlungcancer AT mohammadayalqudah insightsintothemolecularmechanismsmediatingextravasationinbrainmetastasisofbreastcancermelanomaandlungcancer AT rifathamoudi insightsintothemolecularmechanismsmediatingextravasationinbrainmetastasisofbreastcancermelanomaandlungcancer AT raniaharati insightsintothemolecularmechanismsmediatingextravasationinbrainmetastasisofbreastcancermelanomaandlungcancer |