Asset Details
Do you wish to reserve the book?
HIF-1 promotes murine breast cancer brain metastasis by increasing production of integrin β3–containing extracellular vesicles
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
HIF-1 promotes murine breast cancer brain metastasis by increasing production of integrin β3–containing extracellular vesicles
Do you wish to request the book?
HIF-1 promotes murine breast cancer brain metastasis by increasing production of integrin β3–containing extracellular vesicles
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
HIF-1 promotes murine breast cancer brain metastasis by increasing production of integrin β3–containing extracellular vesicles
2025
Overview
Brain metastasis is a major cause of breast cancer (BC) mortality, but the cellular and molecular mechanisms have not been fully elucidated. BC cells must breach the blood-brain barrier in order to colonize the brain. Here, we determined that integrin β3 (ITGB3) expression mediated by hypoxia-inducible factor 1 (HIF-1) plays a critical role in metastasis of BC cells to the brain. Hypoxia stimulated BC cell migration and invasion ex vivo and brain colonization in vivo. Knockdown of either HIF-1α or ITGB3 expression impaired brain colonization by human or mouse BC cells injected into the cardiac left ventricle. Exposure of BC cells to hypoxia increased expression of ITGB3 and its incorporation into small extracellular vesicles (EVs). EVs harvested from the conditioned medium of hypoxic BC cells showed increased retention in the brain after intracardiac injection that was HIF-1α and ITGB3 dependent. EVs from hypoxic BC cells showed binding to brain endothelial cells (ECs), leading to increased EC-BC cell interaction, increased vascular endothelial growth factor receptor 2 signaling, increased EC permeability, and increased transendothelial migration of BC cells. Taken together, our studies implicate HIF-1-stimulated production of ITGB3+ EVs as a key mechanism by which hypoxia promotes BC brain metastasis.
Publisher
American Society for Clinical Investigation
Subject
/ Brain Neoplasms - metabolism
/ Breast Neoplasms - metabolism
/ Breast Neoplasms - pathology
/ Endothelial Cells - metabolism
/ Endothelial Cells - pathology
/ Extracellular Vesicles - genetics
/ Extracellular Vesicles - metabolism
/ Extracellular Vesicles - pathology
/ Female
/ Humans
/ Hypoxia-Inducible Factor 1, alpha Subunit - genetics
/ Hypoxia-Inducible Factor 1, alpha Subunit - metabolism
/ Integrin beta3 - biosynthesis
/ Mammary Neoplasms, Experimental - genetics
/ Mammary Neoplasms, Experimental - metabolism
/ Mammary Neoplasms, Experimental - pathology
/ Mice
/ Neoplasm Proteins - genetics
/ Neoplasm Proteins - metabolism
/ Oncology
