Insights into the Merkel cell phenotype from Merkel cell carcinoma cell lines

Merkel cell carcinoma (MCC) of the skin is an aggressive form of skin cancer and is being seen with increasing incidence in Queensland. We have recently established a number of MCC cell lines and characterized these for growth, morphology, expression of neuroendocrine markers and radiation sensitivity. As a result, cell lines were grouped into four classes by their morphology in a similar way to small cell lung cancer (SCLC) cell lines. Types I and II cell lines grew slowly as tight spherical clusters suspended in the medium, with Type II cell lines less densely packed than the Type I cell lines. Type III cell lines grew as flat 2-dimensional clusters and had shorter doubling times and Type IV cell lines grew as adherent monolayers and had the shortest doubling times. Expression of neuroendocrine markers distinguished those with a classic phenotype from those with a variant one. Mainly morphological Types I and II retained the classic phenotype while Classes III and IV had a variant phenotype. The range of surviving fraction at 2 Gray (SF2 0.2-0.45) seen in MCC cell lines was not as high as seen in SCLC cell lines but the variant ones tended to be more radiation resistant. Examination of POU proteins showed that neuroendocrine phenotype was linked with expression of brn-2, and growth in suspension with brn-3c.