Abstracts
2000 Digestive Disease Week

# 2301 Parathyroid Hormone-Related Protein Expression in Human Pancreatic Adenocarcinoma.
Michael Bouvet, Stephanie R. Nardin, Douglas W. Burton, Cynthia Behling, John M. Carethers, Robert M Hoffman, A. R. Moossa, Leonard J. Deftos, San Diego, CA

Parathyroid hormone-related protein (PTHrP) is expressed in many common malignancies such as breast and prostate cancer and can regulate their growth. Little is known, however, about the role of PTHrP in pancreatic adenocarcinoma. In order to study PTHrP expression in pancreatic cancer, eight human pancreatic carcinoma cell lines were evaluated including 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 amino acid-fragment (1-34), mid-region (38-64), and carboxy-terminal amino-acid fragment (109-141) of PTHrP were used to identify intracellular PTHrP, secreted PTHrP, and for western blotting and immunocytochemical staining for PTHrP from each cell line. Intracellular PTHrP 1-34 was detected in all cell lines by both western blotting and immunoassay at concentrations ranging from 2.6 to 30.5 pg/mg protein. CFPAC-1, derived from a pancreatic liver metastasis, had the highest concentration and MIA PaCa-2, derived from primary pancreatic adenocarcinoma, the lowest. Secretion of PTHrP 1-34 into cell media was also noted for each cell line and paralled intracellular PTHrP 1-34 levels. PTHrP was localized by immunocytochemical staining in the cytoplasm in all but one cell line and both nuclear and cytoplasmic immunostaining was observed in the MIA PaCa-2 and PANC-1 cells. Evidence for differential processing of PTHrP was provided by studies demonstrating that PTHrP 38-64 secretion was highest for BxPC-3 rather than CFPAC-1 while the highest levels of PTHrP 109-141 secretion were seen in Capan-1. Immunostaining from archival tissue of patients with pancreatic adenocarcinoma revealed strong PTHrP staining in 14 of 14 specimens. These results demonstrate that PTHrP is commonly expressed in pancreatic cancer and may play a role in the pathogenesis of this disease.