Introduction Lung cancer is the second most common cancer in the UK with about 42,000 people being diagnosed in 2010 alone (Office of National Statistics, 2012). With a tendency to form invasive metastases coupled with its frequent late stage diagnosis, lung cancer attributes to the largest cause of cancer related mortality worldwide. Despite advances in treatment and care, the five-year mortality rate remains at 90%. There is a desperate need to improve patient survival, which can be achieved partly through improved screening techniques and more importantly by expanding our understanding of the molecular changes associated with lung cancer development and progression.
We investigate the role of a tumour suppressor gene, first identified in lung cancer, tumour suppressor in lung cancer 1 (TSLC1) or cell adhesion molecule 1 (Cadm1) in regulating squamous cell carcinoma (SqCC) growth and metastases.
Methods Cadm1 expression levels were examined using q-PCR analysis on human pre-invasive airway and normal lung tissue collected as part of an on-going UCL/CRUK longitudinal-tracking study (Lung-Surveillance and Lung-SEARCH trials). Cadm1 was introduced into an established SqCC cell line (A431) and in vitro functional assays performed to investigate its effect on tumour growth, progression and invasion. Pre-clinical mice models were used to study the effect of Cadm1 expression in tumour growth and metastatic potential.
Results q-PCR analyses demonstrated that loss of Cadm1 expression is a frequent early event in pre-invasive human airway compared to normal tissue (p = 0.001). Functional assays using A431, with Cadm1 reintroduced, showed Cadm1 expression levels directly associated with a significant decrease in cell proliferation (p = 0.001) over 10 days and significant reduction in invasion (p = 0.001) over 72 hours compared to control A431 cells without Cadm1. Pre-clinical xenograft tumourigenecity experiments in mice showed that Cadm1 expression significantly inhibited tumour growth (p = 0.01) together with a significant reduction in the number of metastases observed (p = 0.01) when compared with the control group.
Conclusion These data suggest that restoration of Cadm1 expression in human squamous cell carcinomas play an important role in regulation of tumour growth and metastasis. Understanding the mechanism through which Cadm1 expression is able to modulate cancer progression maybe therapeutically beneficial.