Endocrine Abstracts

Small cell lung cancer (SCLC) is the most common cause of the ectopic ACTH syndrome and is characterised by rapid growth and poor prognosis. In the ectopic ACTH syndrome, tumours secrete highly elevated levels of the ACTH precursor, proopiomelanocortin (POMC), compared to ACTH itself (Oliver 2003). This study aimed to develop a mouse model of SCLC capable of secreting high levels of POMC and correlate this with viable tumour mass to assess POMC as a potential biomarker.

We have previously identified a panel of SCLC cell lines that express POMC. These tumour cells secrete POMC, but not ACTH, and express other neuroendocrine markers in vitro. When the human SCLC cell line, DMS 79, is grown in vivo, tumours stain positive for POMC and negative for ACTH. Tumours are also positive for additional neuroendocrine markers including neural cell adhesion molecule (N-CAM) and neuron-specific enolase (NSE). Tumour cells found invading into the muscle surrounding the tumour also stained positive for POMC.

Mice bearing DMS79 xenograft tumours exhibit high levels of POMC in the circulation. Over the 4 weeks tumours took to reach 1000 mm³ in size, circulating POMC increased 11-fold. ACTH and corticosterone, although not correlating with tumour growth, both increased in relation to the time tumours were maintained in vivo.

Analysis of viable tumour mass in irradiated versus non-irradiated tumours revealed a strong correlation with POMC levels. Differences in viable cell number were a result of extensive necrosis in irradiated tumours.

These results indicate that POMC, but not ACTH, can act as a reliable indicator of viable tumour mass in patients with SCLC tumours capable of secreting POMC. The neuroendocrine phenotype may also play a role in SCLC tumour cell invasion.

Declaration of funding: Barbara Mawer Studentship, Biotechnology and Biological Sciences Research Council (BBSRC), Manchester Biomedical Research Centre.