Pancreatic cancer stimulates pancreatic stellate cell proliferation and TIMP-1 production through the MAP kinase pathway

Seiya Yoshida, Tokuyasu Yokota, Michael Ujiki, Xian Zhong Ding, Carolyn Pelham, Thomas E. Adrian, Mark S. Talamonti, Richard H. Bell, Woody Denham

Research output: Contribution to journalArticlepeer-review

46 Citations (Scopus)


Pancreatic adenocarcinoma is characterized by an intense desmoplastic reaction that surrounds the tumor. Pancreatic stellate cells (PSCs) are thought to be responsible for production of this extracellular matrix. When activated, PSCs have a myofibroblast phenotype and produce not only components of the extracellular matrix including collagen, fibronectin, and laminin, but also matrix metalloproteinases and tissue inhibitors of metalloproteinases (TIMPs). Since PSCs are found in the stroma surrounding human pancreatic adenocarcinoma, we postulate that pancreatic cancer could impact PSC proliferation and TIMP-1 production. Rat PSCs were isolated and cultured. Isolated PSCs were exposed to PANC-1 conditioned medium (CM) and proliferation, activation of the mitogen-activated protein (MAP) kinase pathway, and TIMP-1 gene induction were determined. Exposure to PANC-1 CM increased PSC DNA synthesis, cell number, and TIMP-1 mRNA (real-time PCR) as well as activating the extracellular-regulated kinase (ERK) 1/2. Inhibition of ERK 1/2 phosphorylation (U0126) prevented the increases in growth and TIMP-1 expression. PANC-1 CM stimulates PSC proliferation and TIMP-1 through the MAP kinase (ERK 1/2) pathway.

Original languageEnglish
Pages (from-to)1241-1245
Number of pages5
JournalBiochemical and Biophysical Research Communications
Issue number4
Publication statusPublished - Oct 29 2004
Externally publishedYes


  • Desmoplasia
  • Mitogen-activated protein kinase
  • Pancreatic cancer
  • Pancreatic stellate cell
  • Tissue inhibitor of metalloproteinase
  • U0126

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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