Pro-gastrin-releasing peptide expression in Ewing sarcoma cells in vitro and in vivo demonstrates its availability as a valuable tumor marker

Abstract

Pro-gastrin-releasing peptide (ProGRP) is the precursor of gastrin-releasing peptide (GRP), a neuropeptide hormone with diverse biological activities. ProGRP is an established tumor marker for small cell lung carcinoma (SCLC). Recently, we reported the usefulness of ProGRP as a tumor marker for Ewing’s sarcoma (ES) family tumors (ESFTs). We performed in vitro and in vivo studies on the expression of ProGRP in ES cell lines to assess the reliability of ProGRP as a tumor marker for ESFTs. High levels of GRP mRNA and ProGRP protein were detected in ES cell lines, including A-673, SK-N-MC, SK-NEP-1, and DMS 53 SCLC cell line, but no expression was detected in SU-CCS-1 clear cell sarcoma cell line. ProGRP expression was also detected in in vivo studies using tumor-bearing athymic mice inoculated with ES and SCLC cell lines. In tumor growth experiment using A-673 cells, plasma ProGRP was detected in all mice one week after tumor cell inoculation. Plasma ProGRP levels increased with increasing tumor size, and surgical resection of the tumor on Day 21 eliminated plasma ProGRP completely. These results demonstrate that ProGRP is produced and released by ES cells and strongly indicate the high ability of ProGRP as a diagnostic marker for ESFTs.