Dissecting the role of the senescent secretome in tumorigenesis

Principal Investigators: Dr Daniel Muñoz-Espín (Cambridge) & Dr Jim Korkola (OHSU)

Funded by: OHSU-CRUK PROJECT Award 2018

Senescence is a cell autonomous response to damage and oncogenic stress resulting in a stable cell cycle arrest. Senescent cells also accumulate with age in multiple tissues, and building evidence suggests they may contribute to inflammatory changes and tumourigenesis by secreting a complex cocktail of paracrine factors, the senescence-associated secretory phenotype (SASP). However, the precise SASP factors remain undefined because the tumour microenvironment is highly complex, and thus assigning functional impact to any single factor remains a challenge. We have developed microenvironment-microarrays (MEMA), a technology that allows us to screen thousands of unique combinations of matrix proteins and soluble ligands for their impact on cellular phenotypes. We propose to use MEMA to identify SASP factors that can drive proliferation, differentiation changes, and increased invasiveness in pre-cancerous and early lung and breast cancer cells.