Pro-opiomelanocortin is a marker of liver and brain metastases from small cell lung cancer xenografts
Suzanne Meredith1, Muhammad Babur1, Ghazala Begum1, Brian Telfer1, Roben Gieling1, Emma Dean2, Caroline Dive2, Kaye Williams1 & Anne White1
Small cell lung cancer (SCLC) is highly aggressive with a particularly poor prognosis. This is due to tumours quickly metastasising and developing chemoresistance. SCLC tumours possess neuroendocrine properties in that they secrete prohormones such as pro-opiomelanocortin (POMC) and pro-gastrin releasing peptide (pro-GRP). These can be detected in the circulation and therefore have potential as biomarkers for prognosis and relapse. The aims of this study are; i) develop a model of SCLC metastasis in vivo, ii) determine if POMC is a biomarker of tumour burden and iii) analyse the presence of POMC in liver and brain metastases.
We have shown that POMC is secreted from 6 of 15 (40%) SCLC cell lines in vitro. The POMC-secreting SCLC cell line, DMS79, was seeded subcutaneously as a xenograft in 9 nude mice. Tumours were identified after 3 days and circulating POMC rapidly increased after day 17. POMC secretion correlated with tumour burden and also with number of days post-inoculation. DMS79 cells were injected i.v. in 4 nude mice, but they did not establish visible tumours up to 79 days and POMC did not increase in the circulation. The POMC non-secreting cell line, H526, grew as a xenograft but POMC concentrations did not increase in the circulation. Micro-metastases were identified by H&E staining in 7 of 8 livers of the DMS79 xenografted mice and POMC positive metastatic areas were detected in 6 of 8 livers by immunohistochemistry. We also saw POMC positive metastases in all brains analysed.
In summary, we have produced a model of SCLC metastasis in vivo and identified POMC in metastatic areas of the liver and brain. This suggests that circulating POMC may be a biomarker of tumour metastasis, which could be used for better prognosis and tailored treatment of SCLC.