Trefoil factor 1 stimulates both pancreatic cancer and stellate cells and increases metastasis

Pancreas. 2011 Aug;40(6):815-22. doi: 10.1097/MPA.0b013e31821f6927.


Objectives: Trefoil factor 1 (TFF1) is a stable secretory protein expressed widely in the gastrointestinal mucosa that is also expressed in pancreatic ductal adenocarcinoma (PDAC). In the current study, we documented the extent and timing of TFF1 expression and investigated the effects of TFF1 on PDAC cells and stellate cells, the primary cells of the PDAC stroma.

Methods: Trefoil factor 1 expression in pancreatic cancer tissues and cell lines was analyzed using microarray, quantitative reverse transcriptase-polymerase chain reaction, and immunohistochemistry. The effects of recombinant TFF1 on cell growth, migration, and invasion of pancreatic cancer cell lines and immortalized human pancreatic stellate cells (HPSCs) were analyzed using MTS and Matrigel-coated invasion chambers. In vivo studies were also conducted in which Mpanc-96 cells stably expressing TFF1 were implanted orthotopically into nude mice.

Results: Trefoil factor 1 was highly increased in preneoplastic lesions. Recombinant TFF1 stimulated motility of both cancer and HPSCs. In contrast, only HPSC cell growth was increased by TFF1. In vivo studies showed that overexpression of TFF1 in PDAC cells did not affect primary tumor growth but greatly increased metastasis.

Conclusions: The present data demonstrate that TFF1 influences both PDAC cells and stellate cells and stimulates metastasis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Base Sequence
  • Carcinoma, Pancreatic Ductal / genetics
  • Carcinoma, Pancreatic Ductal / pathology
  • Carcinoma, Pancreatic Ductal / physiopathology*
  • Carcinoma, Pancreatic Ductal / secondary
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • DNA Primers / genetics
  • Humans
  • Immunohistochemistry
  • Male
  • Mice
  • Mice, Nude
  • Neoplasm Invasiveness
  • Neoplasm Transplantation
  • Oligonucleotide Array Sequence Analysis
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / pathology
  • Pancreatic Neoplasms / physiopathology*
  • Pancreatic Stellate Cells / drug effects
  • Pancreatic Stellate Cells / pathology
  • Pancreatic Stellate Cells / physiology
  • Precancerous Conditions / genetics
  • Precancerous Conditions / pathology
  • Precancerous Conditions / physiopathology
  • Recombinant Proteins / pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transplantation, Heterologous
  • Trefoil Factor-1
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / pharmacology
  • Tumor Suppressor Proteins / physiology*


  • DNA Primers
  • Recombinant Proteins
  • TFF1 protein, human
  • Trefoil Factor-1
  • Tumor Suppressor Proteins