Extracellular Vesicle-Mediated Purinergic Signaling Contributes to Host Microenvironment Plasticity and Metastasis in Triple Negative Breast Cancer

Autor: Suzann Duan, Iain L. O. Buxton, Aidan E. Byrnes, Senny Nordmeier
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Lung Neoplasms
Angiogenesis
Triple Negative Breast Neoplasms
Mice
SCID
Metastasis
lcsh:Chemistry
angiogenesis
Cell Movement
Tumor Microenvironment
lcsh:QH301-705.5
Spectroscopy
Triple-negative breast cancer
education.field_of_study
medicine.diagnostic_test
Chemistry
nucleoside diphosphate kinase
General Medicine
Extracellular vesicle
Purinergic signalling
NM23 Nucleoside Diphosphate Kinases
Nucleoside-diphosphate kinase
Computer Science Applications
Endothelial stem cell
Receptors
Purinergic P2Y
Female
extracellular vesicles
Nucleoside diphosphate kinase A
Signal Transduction
purinergic signaling
exosomes
Catalysis
Article
Flow cytometry
Cell Line
Inorganic Chemistry
Western blot
Cell Line
Tumor
medicine
Animals
Humans
metastasis
Physical and Theoretical Chemistry
education
Molecular Biology
Organic Chemistry
Endothelial Cells
medicine.disease
Microvesicles
lcsh:Biology (General)
lcsh:QD1-999
triple negative breast cancer
Cancer research
Zdroj: International Journal of Molecular Sciences
Volume 22
Issue 2
International Journal of Molecular Sciences, Vol 22, Iss 597, p 597 (2021)
ISSN: 1422-0067
DOI: 10.3390/ijms22020597
Popis: Metastasis accounts for over 90% of cancer-related deaths, yet the mechanisms guiding this process remain unclear. Secreted nucleoside diphosphate kinase A and B (NDPK) support breast cancer metastasis. Proteomic evidence confirms their presence in breast cancer-derived extracellular vesicles (EVs). We investigated the role of EV-associated NDPK in modulating the host microenvironment in favor of pre-metastatic niche formation. We measured NDPK expression and activity in EVs isolated from triple-negative breast cancer (MDA-MB-231) and non-tumorigenic mammary epithelial (HME1) cells using flow cytometry, western blot, and ATP assay. We evaluated the effects of EV-associated NDPK on endothelial cell migration, vascular remodeling, and metastasis. We further assessed MDA-MB-231 EV-induced proteomic changes in support of pre-metastatic lung niche formation. NDPK-B expression and phosphotransferase activity were enriched in MDA-MB-231 EVs that promote vascular endothelial cell migration and disrupt monolayer integrity. MDA-MB-231 EV-treated mice demonstrate pulmonary vascular leakage and enhanced experimental lung metastasis, whereas treatment with an NDPK inhibitor or a P2Y1 purinoreceptor antagonist blunts these effects. We identified perturbations to the purinergic signaling pathway in experimental lungs, lending evidence to support a role for EV-associated NDPK-B in lung pre-metastatic niche formation and metastatic outgrowth. These studies prompt further evaluation of NDPK-mediated EV signaling using targeted genetic silencing approaches.
Databáze: OpenAIRE
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