The extracellular matrix differentially regulates the expression of PTHrP and the PTH/PTHrP receptor in FG pancreatic cancer cells

Pancreas. 2004 Aug;29(2):85-92. doi: 10.1097/00006676-200408000-00001.


Objectives: 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.

Method and 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).

Conclusion: 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.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology*
  • Animals
  • Cattle
  • Cell Division
  • Cell Line, Tumor / drug effects
  • Cell Line, Tumor / metabolism
  • Collagen / pharmacology
  • Extracellular Matrix / physiology*
  • Extracellular Matrix Proteins / pharmacology*
  • Extracellular Matrix Proteins / physiology
  • Fibronectins / pharmacology
  • Gene Expression Regulation, Neoplastic* / drug effects
  • Humans
  • Intercellular Adhesion Molecule-1 / pharmacology
  • Laminin / pharmacology
  • Mice
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology*
  • Parathyroid Hormone-Related Protein / biosynthesis*
  • Parathyroid Hormone-Related Protein / genetics
  • Protein Isoforms / pharmacology
  • Receptor, Parathyroid Hormone, Type 1 / biosynthesis*
  • Receptor, Parathyroid Hormone, Type 1 / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tenascin / pharmacology
  • Vascular Cell Adhesion Molecule-1 / pharmacology
  • Vitronectin / pharmacology


  • Extracellular Matrix Proteins
  • Fibronectins
  • Laminin
  • Neoplasm Proteins
  • Parathyroid Hormone-Related Protein
  • Protein Isoforms
  • Receptor, Parathyroid Hormone, Type 1
  • Tenascin
  • Vascular Cell Adhesion Molecule-1
  • Vitronectin
  • Intercellular Adhesion Molecule-1
  • Collagen