Maria Georgiadou

Lung cancer is the leading cause of morbidity and mortality worldwide. Unfortunately, most lung cancers present as stage IV attributed to metastatic disease, which is associated with increased symptom burden and poor survival. Novel and potent therapy options have transformed the treatment of some subsets of lung cancer; nevertheless, the clinical benefit is still limited to a minority of patients reflecting the need to better understand the underlying biology of the disease. This limited response is mainly attributed to therapeutic resistance, which is manifested as local or distant disease recurrence.

Stiffness is a biophysical property of the ECM that modulates cellular functions, including proliferation, invasion, differentiation, and it may affect therapeutic responses. The ability of the cells to sense tissue stiffness and convert these mechanical cues into intracellular changes is termed mechanotrasduction. While it is well established that ECM stiffness influences the behaviour of normal cells the role of matrix stiffness in transformed cells – and more precisely in lung cancer cells – remains largely unclear.

We are using hydrogels with tuneable stiffness to study the impact of ECM rigidity on lung cancer cells growth, motility, response to drug treatment and effects on cell metabolism.

Figure 1. (A) Schematic of the fabrication of hydrogels with tuneable stiffness; (B) Representative images of HCC827 lung cancer cells plated on soft (left) or stiff (right) hydrogels and stained for the actin marker phalloidin and active ?1-integrin antibody (12G10).

Research aims:

1. To understand how extracellular matrix stiffness regulates lung cancer cell growth, migratory behaviour and drug resistance
2. To identify novel therapeutic vulnerabilities in lung cancer cells treated with targeted therapies