title: Pleiotrophin can be rate-limiting for pancreatic cancer cell growth.
abstract: Pancreatic cancer is one of the most aggressive malignant tumors, with an overall survival rate of 2%. The identification of growth factors that contribute to the malignant phenotype can help to identify new targets for therapy. In this study, we analyzed the growth factor pleiotrophin (PTN) that was originally described as a developmentally regulated cytokine during early embryogenesis. More recently, PTN was found to be overexpressed in a variety of neuroectodermal tumors and described as an essential angiogenic growth factor in choriocarcinoma and melanoma, promoting metastatic growth. Recently, we discovered high expression levels of PTN in patients with gastrointestinal malignancies, particularly in those patients with pancreatic cancer. However, it is not known whether PTN is a contributor to the growth of pancreatic cancer or is only a bystander. We used ribozymes to deplete PTN mRNA from Colo357 pancreatic cancer cells and studied the resulting phenotype. The reduction of PTN resulted in a decrease in the proliferation rate, soft agar colony formation, and tumor growth in animals. Supplementation of cells with PTN partially reversed the ribozyme effect. The autocrine function of PTN was confirmed by using PTN-binding antibodies that inhibited the proliferation rate by 50% in Colo357 cells but also in a different pancreatic cancer cell line, Panc89. Our study identifies PTN as a new and essential growth factor for pancreatic cancer. Due to the restricted expression pattern of PTN in adults, PTN is suggested as a target for pancreatic cancer therapy.
authors.affiliation: Lombardi Cancer Center, Georgetown University Medical Center, Washington, DC, 20007, USA.
authors.forename: D
authors.initials: D
authors.lastname: Weber
authors.forename: H J
authors.initials: HJ
authors.lastname: Klomp
authors.forename: F
authors.initials: F
authors.lastname: Czubayko
authors.forename: A
authors.initials: A
authors.lastname: Wellstein
authors.forename: H
authors.initials: H
authors.lastname: Juhl
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D000906:Antibodies / Q000378:metabolism / Q000494:pharmacology; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D054278:Embryonal Carcinoma Stem Cells; D005260:Female; D006133:Growth Substances / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured
chemical_list: D000906:Antibodies; D002352:Carrier Proteins; D016207:Cytokines; D006133:Growth Substances; C066845:pleiotrophin