The role of actin isoforms in cancer adhesion of the endothelium during metastasis

Metastasis is the leading cause of death in cancer patients; however, the majority of research has been conducted on primary cancer. Metastasis is the spread of cancer cells by the invasion and migration through local tissue into the blood and lymphatic vessels, relocating to a secondary site using these as transport mechanisms. An important part of metastasis is the binding of cancer cells to the endothelial blood vessel lining. Here, adhesion and migration are key metastatic aspects involving the cancer cell undergoing morphological changes, such as cell protrusions called lamellipodia. Cytoplasmic actin has a role in the formation of these structures as well as one specific isoform, γactin, themselves being associated with cancer. Extracellular vesicles (EVs) are small lipid-bound vesicles that act as communicators between cells carrying biological cargo. EVs have been implicated in supporting the formation of the metastatic niche and preparing for incoming circulating cancer cells promoting growth factor release in the local tissue. Common breast cancer models; healthy (hTERT-HME1), primary (BT-474) and metastatic (MCF7) breast epithelial tissue were tested for the presence of cell and EV surface γ-actin using immunocytofluorescence and flow cytometry. Once the EVs were characterised, different variations of cell line EVs and cells were treated on endothelial cells to quantify cell binding with and without antibody blocking. This showed that γ-actin was on the surface of various cell lines and their EVs. Masking surface γactin with an antibody treated onto cells resulted in significantly lower numbers of breast epithelial cells binding to the endothelial monolayer. Following this breast epithelial cells incubated with EVs for an hour prior to endothelial monolayer exposure showed increases in cell binding whilst incubation for 3 minutes resulted in a decrease in the number of cells bound. These findings may suggest that surface γ-actin on cells and EVs could have a roll in breast epithelial binding to the endothelium. Further research into this could provide promising patient diagnostics in the future for patients with a history of breast cancer to screen for the presence of metastases

Grantor dc:publisher

Oxford Brookes University

Author dc:creator

• Airstone, Bethy

Contributors dc:contributor

• Pink, Ryan
• Brooks, Susan
• Samuel, Priya

Statement dc:rights

• All rights reserved

Language dc:language

en

DOI dc:identifier

https://doi.org/10.24384/tkwg-ym63

OAI identifier oai:identifier

tle:51fede22-d57a-4b5f-b83f-9c075c50f8d6:d6bd9758-527a-46cd-bfe2-c433766e8fca:1