The role of extracellular vesicles in senescence surveillance

Principal Investigators: Dr Matthew Hoare, University of Cambridge and Dr Ferdinando Pucci, Oregon Health and Science University

Funded by: CRUK-OHSU Early Detection Project Award

Cellular senescence is a stress-responsive tumour suppressor mechanism. Senescent cells accumulate in chronic inflammatory cancer-prone tissues. Senescent cells have profound non-autonomous effects upon immunocytes, driving their own destruction. Failure of this immune reaction with persistent senescence leads to tumorigenesis. Understanding how senescent cells communicate with their microenvironment represents a promising strategy to detect incipient tumorigenesis.

Extracellular vesicles (EVs) are nanometer-scale membrane-bound vesicles, emitted from most cells types and are detectable in the circulation. Emerging evidence suggests they play a significant role in non-autonomous signalling. Tumor-derived EVs can be engulfed by and modulate the function of macrophages in distant lymph nodes. Previous in vitro studies have shown that senescent cells secrete EVs and that these carry specific nucleic acid and protein cargos, driving non-autonomous signaling. Nothing is known about senescent cell-derived extracellular vesicles (sEVs) in vivo.

The aim of the project is to define a signature of sEVs, define their fate and precise effect upon the immune system before validating the findings in patients.