title: The extracellular matrix differentially regulates the expression of PTHrP and the PTH/PTHrP receptor in FG pancreatic cancer cells.
abstract: OBJECTIVE
  Previous studies by our laboratory have demonstrated that parathyroid hormone-related protein (PTHrP) and its receptor (PTH/PTHrP receptor) are commonly expressed in pancreatic cancer and suggest their participation in the progression of this devastating disease. It has also been demonstrated that one of the major hallmarks of pancreatic adenocarcinoma is an increased production of the extracellular matrix (ECM), a critical regulator of diverse cellular processes such as differentiation, proliferation, and angiogenesis. The present study focused on the relationship between the PTHrP and ECM axes in the pathobiology of pancreatic cancer.
  
  
  RESULTS
  Using the FG pancreatic adenocarcinoma cell line, we demonstrate a significant inverse correlation between FG cell proliferation and PTHrP expression that depended on the ECM protein on which the cells were cultured (P < 0.05). Generally, ECM proteins that promoted the strongest proliferation, including type I collagen, type IV collagen, and laminin, resulted in decreased expression of PTHrP. Conversely, ECM proteins that promoted the weakest proliferation, including fibronectin, vitronectin, and BSA, resulted in increased expression of PTHrP. A similar trend was found between FG cell proliferation and the PTH/PTHrP receptor expression, with Pearson correlation coefficients of 0.480 (mRNA) and -0.591 (protein).
  
  
  CONCLUSIONS
  These observations demonstrate a unique functional relationship between the ECM and PTHrP axes and have important implications for our understanding of the complex mechanisms responsible for the progression of pancreatic cancer and its metastases.
authors.affiliation: Department of Surgery, University of California, San Diego and San Diego Veterans Affairs Medical Center, San Diego, California 92161, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Grzesiak
authors.forename: Paul
authors.initials: P
authors.lastname: Clopton
authors.forename: Cheryl
authors.initials: C
authors.lastname: Chalberg
authors.forename: Kathy
authors.initials: K
authors.lastname: Smith
authors.forename: Douglas W
authors.initials: DW
authors.lastname: Burton
authors.forename: Steve
authors.initials: S
authors.lastname: Silletti
authors.forename: A R
authors.initials: AR
authors.lastname: Moossa
authors.forename: Leonard J
authors.initials: LJ
authors.lastname: Deftos
authors.forename: Michael
authors.initials: M
authors.lastname: Bouvet
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D002417:Cattle; D002455:Cell Division; D045744:Cell Line, Tumor / Q000187:drug effects / Q000378:metabolism; D003094:Collagen / Q000494:pharmacology; D005109:Extracellular Matrix / Q000502:physiology*; D016326:Extracellular Matrix Proteins / Q000494:pharmacology* / Q000502:physiology; D005353:Fibronectins / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000494:pharmacology; D007797:Laminin / Q000494:pharmacology; D051379:Mice; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D044162:Parathyroid Hormone-Related Protein / Q000096:biosynthesis* / Q000235:genetics; D020033:Protein Isoforms / Q000494:pharmacology; D044168:Receptor, Parathyroid Hormone, Type 1 / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019063:Tenascin / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000494:pharmacology; D019096:Vitronectin / Q000494:pharmacology
chemical_list: D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D007797:Laminin; D009363:Neoplasm Proteins; D044162:Parathyroid Hormone-Related Protein; D020033:Protein Isoforms; D044168:Receptor, Parathyroid Hormone, Type 1; D019063:Tenascin; D019010:Vascular Cell Adhesion Molecule-1; D019096:Vitronectin; D018799:Intercellular Adhesion Molecule-1; D003094:Collagen