Regulation of exosome release from mammary epithelial and breast cancer cells - a new regulatory pathway.
OBJECTIVE
Exosomes are small 50-100nm sized extracellular vesicles released from normal and tumour cells and are a source of a new intercellular communication pathway. Tumour exosomes promote tumour growth and progression. What regulates the release and homoeostatic levels of exosomes, in cancer, in body fluids remains undefined.


METHODS
We utilised a human mammary epithelial cell line (HMEC B42) and a breast cancer cell line derived from it (B42 clone 16) to investigate exosome production and regulation. Exosome numbers were quantified using a Nanosight LM10 and measured in culture supernatants in the absence and presence of exosomes in the medium. Concentrated suspensions of exosomes from the normal mammary epithelial cells, the breast cancer cells and bladder cancer cells were used. The interaction of exosomes with tumour cells was also investigated using fluorescently labelled exosomes.


RESULTS
Exosome release from normal human mammary epithelial cells and breast cancer cells is regulated by the presence of exosomes, derived from their own cells, in the extracellular environment of the cells. Exosomes from normal mammary epithelial cells also inhibit exosome secretion by breast cancer cells, which occurs in a tissue specific manner. Labelled exosomes from mammary epithelial cells are internalised into the tumour cells implicating a dynamic equilibrium and suggesting a mechanism for feedback control.


CONCLUSIONS
These data suggest a previously unknown novel feedback regulatory mechanism for controlling exosome release, which may highlight a new therapeutic approach to controlling the deleterious effects of tumour exosomes. This regulatory mechanism is likely to be generic to other tumours.
School of Medicine, Medical & Biological Sciences Building, University of St Andrews, KY16 9TF Scotland, UK. Electronic address: acr1@st-andrews.ac.uk.
Andrew
A
Riches
School of Medicine, Medical & Biological Sciences Building, University of St Andrews, KY16 9TF Scotland, UK.
Elaine
E
Campbell
School of Biology, Medical & Biological Sciences Building, University of St Andrews, KY16 9TF Scotland, UK.
Eva
E
Borger
School of Medicine, Medical & Biological Sciences Building, University of St Andrews, KY16 9TF Scotland, UK.
Simon
S
Powis
D015153:Blotting, Western; D001943:Breast Neoplasms / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000737:chemistry / Q000378:metabolism*; D055354:Exosomes / Q000737:chemistry / Q000378:metabolism*; D005110:Extracellular Space / Q000737:chemistry / Q000378:metabolism; D005260:Female; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D042361:Mammary Glands, Human / Q000166:cytology*; D018613:Microscopy, Confocal; D009930:Organic Chemicals / Q000737:chemistry; D015398:Signal Transduction; D013997:Time Factors
D005456:Fluorescent Dyes; D009930:Organic Chemicals; C070080:PKH 26
Breast cancer; Exosomes; Mammary epithelial cells; Regulation