Human pancreatic adenocarcinomas express parathyroid hormone-related protein

PTH-related protein (PTHrP) is expressed in many common malignancies such a s breast and prostate cancer and can regulate their growth. Little is known , however, about the role of PTHrP in pancreatic adenocarcinoma. To study P THrP in pancreatic exocrine cancer, we studied its expression in pancreatic cancer cell lines and surgical specimens. Eight human pancreatic adenocarc inoma cell lines were evaluated: AsPC-1, BxPC-3, Capan-1, CFPAC-1, MIA PaCa -2, PANC-1, PANC-28, and PANC-48. Murine monoclonal antibodies to the amino -terminal (1-34), mid-region (38-64), and carboxyl-terminal peptides (109-1 41) of PTHrP were used to identify cellular PTHrP and secreted PTHrP includ ing Western blotting and immunocytochemical staining for PTHrP from each ce ll line. Cellular PTHrP was detected in all cell line extracts by both West ern blotting and immunoassay. CFPAC-1, derived from a pancreatic liver meta stasis, had the highest concentration of PTHrP, and MIA PaCa-2, derived fro m primary pancreatic adenocarcinoma, had the lowest. PTHrP mas localized by immunocytochemical staining in the cytoplasm in all but one cell line, and both nuclear and cytoplasmic immunostaining were observed in the MIA PaCa- 2 and PANC-1 cells. Secretion of PTHrP into cell medium was also observed f or each cell line and paralleled intracellular PTHrP levels. Evidence for d ifferential processing of PTHrP expression was provided by studies demonstr ating different patterns of PTHrP among the cell lines when assessed by PTH rP immunoassays directed against different PTHrP peptides. In specific, PTH rP secretion measured by a PTHrP-(38-64) assay was highest for BxPC-3, wher eas the highest levels of secreted PTHrP-(109-141) occurred in CFPAC-1 and PANC-1. Growth of AsPC-1 cells Nas stimulated in a dose-dependent manner by PTHrP-(1-34). Immunostaining from archival tissue of patients with pancrea tic adenocarcinoma revealed strong PTHrP expression in all 14 specimens. Al l patients were euealcemic preoperatively. These results demonstrate that P THrP is commonly expressed in pancreatic cancer. Our data suggest that PTHr P may have,growth-regulating properties in pancreatic adenocarcinoma cells, but further studies are required.