PUBLICATION
Adipocytes Promote Early Steps of Breast Cancer Cell Dissemination via Interleukin-8.
- Authors
- Vazquez Rodriguez, G., Abrahamsson, A., Jensen, L.D.E., Dabrosin, C.
- ID
- ZDB-PUB-180816-5
- Date
- 2018
- Source
- Frontiers in immunology 9: 1767 (Journal)
- Registered Authors
- Keywords
- angiogenesis, breast cancer, inflammation, microdialysis, zebrafish
- MeSH Terms
-
- Adipocytes/metabolism*
- Aged
- Aged, 80 and over
- Animals
- Antineoplastic Agents, Immunological/pharmacology
- Biomarkers
- Breast Neoplasms/drug therapy
- Breast Neoplasms/metabolism*
- Breast Neoplasms/pathology*
- Cell Line, Tumor
- Cell Movement
- Cytokines/metabolism
- Disease Models, Animal
- Female
- Humans
- Interleukin-8/antagonists & inhibitors
- Interleukin-8/metabolism*
- Middle Aged
- Neoplasm Grading
- Neoplasm Metastasis
- Neovascularization, Pathologic
- Neutrophil Infiltration
- Tumor Burden
- Vascular Endothelial Growth Factor A/antagonists & inhibitors
- Vascular Endothelial Growth Factor A/metabolism
- Xenograft Model Antitumor Assays
- Zebrafish
- PubMed
- 30105032 Full text @ Front Immunol
Citation
Vazquez Rodriguez, G., Abrahamsson, A., Jensen, L.D.E., Dabrosin, C. (2018) Adipocytes Promote Early Steps of Breast Cancer Cell Dissemination via Interleukin-8.. Frontiers in immunology. 9:1767.
Abstract
Fat is a major tissue component in human breast cancer (BC). Whether breast adipocytes (BAd) affect early stages of BC metastasis is yet unknown. BC progression is dependent on angiogenesis and inflammation, and interleukin-8 (IL-8) and vascular endothelial growth factor (VEGF) are key regulators of these events. Here, we show that BAd increased the dissemination of estrogen receptor positive BC cells (BCC) in vivo in the zebrafish model of metastasis, while dissemination of the more aggressive and metastatic BCC such as estrogen receptor negative was unaffected. While anti-VEGF and anti-IL-8 exhibited equal inhibition of angiogenesis at the primary tumor site, anti-IL-8 reduced BCC dissemination whereas anti-VEGF had minor effects on this early metastatic event. Mechanistically, overexpression of cell-adhesion molecules in BCC and neutrophils via IL-8 increased the dissemination of BCC. Importantly, the extracellular in vivo levels of IL-8 were 40-fold higher than those of VEGF in human BC. Our results suggest that IL-8 is a clinical relevant and promising therapeutic target for human BC.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping